NUCLEIC ACIDS AND CORRESPONDING PROTEINS ENTITLED 109P1 D4 USEFUL IN TREATMENT AND DETECTION OF CANCER STATEMENT OF RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSORED RESEARCH Not applicable.

FIELD OF THE INVENTION The invention described herein relates to genes and their encoded proteins, termed 109P1D4 and variants thereof, expressed in certain cancers, and to diagnostic and therapeutic methods and compositions useful in the management of cancers that express 109P1D4.

BACKGROUND OF THE INVENTION Cancer is the second leading cause of human death next to coronary disease. Worldwide, millions of people die from cancer every year. In the United States alone, as reported by the American Cancer Society, cancer causes the death of well over a half-million people annually, with over 1. 2 million new cases diagnosed per year. While deaths from heart disease have been declining significantly, those resulting from cancer generally are on the rise. In the early part of the next century, cancer is predicted to become the leading cause of death.

Worldwide, several cancers stand out as the leading killers. In particular, carcinomas of the lung, prostate, breast, colon, pancreas, and ovary represent the primary causes of cancer death. These and virtually all other carcinomas share a common lethal feature. With very few exceptions, metastatic disease from a carcinoma is fatal. Moreover, even for those cancer patients who initially survive their primary cancers, common experience has shown that their lives are dramatically altered. Many cancer patients experience strong anxieties driven by the awareness of the potential for recurrence or treatment failure. Many cancer patients experience physical debilitations following treatment. Furthermore, many cancer patients experience a recurrence.

Worldwide, prostate cancer is the fourth most prevalent cancer in men. In North America and Northern Europe, it is by far the most common cancer in males and is the second leading cause of cancer death in men. In the United States alone, well over 30, 000 men die annually of this disease-second only to lung cancer. Despite the magnitude of these figures, there is still no effective treatment for metastatic prostate cancer. Surgical prostatectomy, radiation therapy, hormone ablation therapy, surgical castration and chemotherapy continue to be the main treatment modalities.

Unfortunately, these treatments are ineffective for many and are often associated with undesirable consequences.

On the diagnostic front, the lack of a prostate tumor marker that can accurately detect early-stage, localized tumors remains a significant limitation in the diagnosis and management of this disease. Although the serum prostate specific antigen (PSA) assay has been a very useful tool, however its specificity and general utility is widely regarded as lacking in several important respects.

Progress in identifying additional specific markers for prostate cancer has been improved by the generation of prostate cancer xenografts that can recapitulate different stages of the disease in mice. The LAPC (Los Angeles Prostate Cancer) xenografts are prostate cancer xenografts that have survived passage in severe combined immune deficient (SCID) mice and have exhibited the capacity to mimic the transition from androgen dependence to androgen independence (Klein et al., 1997, Nat. Med. 3 : 402). More recently identified prostate cancer markers include PCTA-1 (Su et al., 1996, Proc. Natl.

Acad. Sci. USA 93 : 7252), prostate-specific membrane (PSM) antigen (Pinto et al., Clin Cancer Res 1996 Sep 2 (9) : 1445- 51), STEAP (Hubert, et al., Proc Natl Acad Sci U S A. 1999 Dec 7 ; 96 (25) : 14523-8) and prostate stem cell antigen (PSCA) (Reiter et al., 1998, Proc. Natl. Acad. Sci. USA 95 : 1735).

While previously identified markers such as PSA, PSM, PCTA and PSCA have facilitated efforts to diagnose and treat prostate cancer, there is need for the identification of additional markers and therapeutic targets for prostate and related cancers in order to further improve diagnosis and therapy.

Renal cell carcinoma (RCC) accounts for approximately 3 percent of adult malignancies. Once adenomas reach a diameter of 2 to 3 cm, malignant potential exists. In the adult, the two principal malignant renal tumors are renal cell adenocarcinoma and transitional cell carcinoma of the renal pelvis or ureter. The incidence of renal cell adenocarcinoma is estimated at more than 29, 000 cases in the United States, and more than 11, 600 patients died of this disease in 1998. Transitional cell carcinoma is less frequent, with an incidence of approximately 500 cases per year in the United States.

Surgery has been the primary therapy for renal cell adenocarcinoma for many decades. Until recently, metastatic disease has been refractory to any systemic therapy. With recent developments in systemic therapies, particularly immunotherapies, metastatic renal cell carcinoma may be approached aggressively in appropriate patients with a possibility of durable responses. Nevertheless, there is a remaining need for effective therapies for these patients.

Of all new cases of cancer in the United States, bladder cancer represents approximately 5 percent in men (fifth most common neoplasm) and 3 percent in women (eighth most common neoplasm). The incidence is increasing slowly, concurrent with an increasing older population. In 1998, there was an estimated 54, 500 cases, including 39, 500 in men and 15, 000 in women. The age-adjusted incidence in the United States is 32 per 100, 000 for men and eight per 100, 000 in women. The historic male/female ratio of 3 : 1 may be decreasing related to smoking patterns in women. There were an estimated 11, 000 deaths from bladder cancer in 1998 (7, 800 in men and 3, 900 in women). Bladder cancer incidence and mortality strongly increase with age and will be an increasing problem as the population becomes more elderly.

Most bladder cancers recur in the bladder. Bladder cancer is managed with a combination of transurethral resection of the bladder (TUR) and intravesical chemotherapy or immunotherapy. The multifocal and recurrent nature of bladder cancer points out the limitations of TUR. Most muscle-invasive cancers are not cured by TUR alone. Radical cystectomy and urinary diversion is the most effective means to eliminate the cancer but carry an undeniable impact on urinary and sexual function. There continues to be a significant need for treatment modalities that are beneficial for bladder cancer patients.

An estimated 130, 200 cases of colorectal cancer occurred in 2000 in the United States, including 93, 800 cases of colon cancer and 36, 400 of rectal cancer. Colorectal cancers are the third most common cancers in men and women.

Incidence rates declined significantly during 1992-1996 (-2. 1 % per year). Research suggests that these declines have been due to increased screening and polyp removal, preventing progression of polyps to invasive cancers. There were an estimated 56, 300 deaths (47, 700 from colon cancer, 8, 600 from rectal cancer) in 2000, accounting for about 11 % of all U. S. cancer deaths.

At present, surgery is the most common form of therapy for colorectal cancer, and for cancers that have not spread, it is frequently curative. Chemotherapy, or chemotherapy plus radiation, is given before or after surgery to most patients whose cancer has deeply perforated the bowel wall or has spread to the lymph nodes. A permanent colostomy (creation of an abdominal opening for elimination of body wastes) is occasionally needed for colon cancer and is infrequently required for rectal cancer. There continues to be a need for effective diagnostic and treatment modalities for colorectal cancer.

There were an estimated 164, 100 new cases of lung and bronchial cancer in 2000, accounting for 14% of all U. S. cancer diagnoses. The incidence rate of lung and bronchial cancer is declining significantly in men, from a high of 86. 5 per 100, 000 in 1984 to 70. 0 in 1996. In the 1990s, the rate of increase among women began to slow. In 1996, the incidence rate in women was 42. 3 per 100, 000.

Lung and bronchial cancer caused an estimated 156, 900 deaths in 2000, accounting for 28% of all cancer deaths.

During 1992-1996, mortality from lung cancer declined significantly among men (-1. 7% per year) while rates for women were still significantly increasing (0. 9% per year). Since 1987, more women have died each year of lung cancer than breast cancer, which, for over 40 years, was the major cause of cancer death in women. Decreasing lung cancer incidence and mortality rates most likely resulted from decreased smoking rates over the previous 30 years ; however, decreasing smoking patterns among women lag behind those of men. Of concern, although the declines in adult tobacco use have slowed, tobacco use in youth is increasing again.

Treatment options for lung and bronchial cancer are determined by the type and stage of the cancer and include surgery, radiation therapy, and chemotherapy. For many localized cancers, surgery is usually the treatment of choice.

Because the disease has usually spread by the time it is discovered, radiation therapy and chemotherapy are often needed in combination with surgery. Chemotherapy alone or combined with radiation is the treatment of choice for small cell lung cancer ; on this regimen, a large percentage of patients experience remission, which in some cases is long lasting. There is however, an ongoing need for effective treatment and diagnostic approaches for lung and bronchial cancers.

An estimated 182, 800 new invasive cases of breast cancer were expected to occur among women in the United States during 2000. Additionally, about 1, 400 new cases of breast cancer were expected to be diagnosed in men in 2000.

After increasing about 4% per year in the 1980s, breast cancer incidence rates in women have leveled off in the 1990s to about 110. 6 cases per 100, 000.

In the U. S. alone, there were an estimated 41, 200 deaths (40, 800 women, 400 men) in 2000 due to breast cancer.

Breast cancer ranks second among cancer deaths in women. According to the most recent data, mortality rates declined significantly during 1992-1996 with the largest decreases in younger women, both white and black. These decreases were probably the result of earlier detection and improved treatment.

Taking into account the medical circumstances and the patient's preferences, treatment of breast cancer may involve lumpectomy (local removal of the tumor) and removal of the lymph nodes under the arm ; mastectomy (surgical removal of the breast) and removal of the lymph nodes under the arm ; radiation therapy ; chemotherapy ; or hormone therapy.

Often, two or more methods are used in combination. Numerous studies have shown that, for early stage disease, long-term survival rates after lumpectomy plus radiotherapy are similar to survival rates after modified radical mastectomy. Significant advances in reconstruction techniques provide several options for breast reconstruction after mastectomy. Recently, such reconstruction has been done at the same time as the mastectomy.

Local excision of ductal carcinoma in situ (DCIS) with adequate amounts of surrounding normal breast tissue may prevent the local recurrence of the DCIS. Radiation to the breast and/or tamoxifen may reduce the chance of DCIS occurring in the remaining breast tissue. This is important because DCIS, if left untreated, may develop into invasive breast cancer. Nevertheless, there are serious side effects or sequelae to these treatments. There is, therefore, a need for efficacious breast cancer treatments.

There were an estimated 23, 100 new cases of ovarian cancer in the United States in 2000 It accounts for 4% of all cancers among women and ranks second among gynecologic cancers. During 1992-1996, ovarian cancer incidence rates were significantly declining. Consequent to ovarian cancer, there were an estimated 14, 000 deaths in 2000. Ovarian cancer causes more deaths than any other cancer of the female reproductive system.

Surgery, radiation therapy, and chemotherapy are treatment options for ovarian cancer. Surgery usually includes the removal of one or both ovaries, the fallopian tubes (salpingo-oophorectomy), and the uterus (hysterectomy). In some very early tumors, only the involved ovary will be removed, especially in young women who wish to have children. In advanced disease, an attempt is made to remove all intra-abdominal disease to enhance the effect of chemotherapy. There continues to be an important need for effective treatment options for ovarian cancer.

There were an estimated 28, 300 new cases of pancreatic cancer in the United States in 2000. Over the past 20 years, rates of pancreatic cancer have declined in men. Rates among women have remained approximately constant but may be beginning to decline. Pancreatic cancer caused an estimated 28, 200 deaths in 2000 in the United States. Over the past 20 years, there has been a slight but significant decrease in mortality rates among men (about-0. 9% per year) while rates have increased slightly among women.

Surgery, radiation therapy, and chemotherapy are treatment options for pancreatic cancer. These treatment options can extend survival and/or relieve symptoms in many patients but are not likely to produce a cure for most. There is a significant need for additional therapeutic and diagnostic options for pancreatic cancer.

SUMMARY OF THE INVENTION The present invention relates to a gene, designated 109P1D4, that has now been found to be over-expressed in the cancer (s) listed in Table I. Northern blot expression analysis of 109P1D4 gene expression in normal tissues shows a restricted expression pattern in adult tissues. The nucleotide (Figure 2) and amino acid (Figure 2, and Figure 3) sequences of 109P1 D4 are provided. The tissue-related profile of 109P1 D4 in normal adult tissues, combined with the over-expression observed in the tissues listed in Table I, shows that 109P1 D4 is aberrant over-expressed in at least some cancers, and thus serves as a useful diagnostic, prophylactic, prognostic, and/or therapeutic target for cancers of the tissue (s) such as those listed in Table I.

The invention provides polynucleotides corresponding or complementary to all or part of the 109P1 D4 genes, mRNAs, and/or coding sequences, preferably in isolated form, including polynucleotides encoding 109P1 D4-related proteins and fragments of 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, or more than 25 contiguous amino acids ; at least 30, 35, 40, 45, 50, 55, 60, 65, 70, 80, 85, 90, 95, 100 or more than 100 contiguous amino acids of a 109P1 D4-related protein, as well as the peptides/proteins themselves ; DNA, RNA, DNA/RNA hybrids, and related molecules, polynucleotides or oligonucleotides complementary or having at least a 90% homology to the 109P1 D4 genes or mRNA sequences or parts thereof, and polynucleotides or oligonucleotides that hybridize to the 109P1 D4 genes, mRNAs, or to 109P1D4-encoding polynucleotides. Also provided are means for isolating cDNAs and the genes encoding 109P1 D4.

Recombinant DNA molecules containing 109P1 D4 polynucleotides, cells transformed or transduced with such molecules, and host-vector systems for the expression of 109P1 D4 gene products are also provided. The invention further provides antibodies that bind to 109P1 D4 proteins and polypeptide fragments thereof, including polyclonal and monoclonal antibodies, murine and other mammalian antibodies, chimeric antibodies, humanized and fully human antibodies, and antibodies labeled with a detectable marker or therapeutic agent. in certain embodiments, there is a proviso that the entire nucleic acid sequence of Figure 2 is not encoded and/or the entire amino acid sequence of Figure 2 is not prepared. In certain embodiments, the entire nucleic acid sequence of Figure 2 is encoded and/or the entire amino acid sequence of Figure 2 is prepared, either of which are in respective human unit dose forms.

The invention further provides methods for detecting the presence and status of 109P1 D4 polynucleotides and proteins in various biological samples, as well as methods for identifying cells that express 109P1 D4. A typical embodiment of this invention provides methods for monitoring 109P1 D4 gene products in a tissue or hematology sample having or suspected of having some form of growth dysregulation such as cancer.

The invention further provides various immunogenic or therapeutic compositions and strategies for treating cancers that express 109P1D4 such as cancers of tissues listed in Table 1, including therapies aimed at inhibiting the transcription, translation, processing or function of 109P1 D4 as well as cancer vaccines. In one aspect, the invention provides compositions, and methods comprising them, for treating a cancer that expresses 109P1 D4 in a human subject wherein the composition comprises a carrier suitable for human use and a human unit dose of one or more than one agent that inhibits the production or function of 109P1 D4. Preferably, the carrier is a uniquely human carrier. In another aspect of the invention, the agent is a moiety that is immunoreactive with 109P1 D4 protein. Non-limiting examples of such moieties include, but are not limited to, antibodies (such as single chain, monoclonal, polyclonal, humanized, chimeric, or human antibodies), functional equivalents thereof (whether naturally occurring or synthetic), and combinations thereof. The antibodies can be conjugated to a diagnostic or therapeutic moiety. In another aspect, the agent is a small molecule as defined herein.

In another aspect, the agent comprises one or more than one peptide which comprises a cytotoxic T lymphocyte (CTL) epitope that binds an HLA class I molecule in a human to elicit a CTL response to 109P1 D4 and/or one or more than one peptide which comprises a helper T lymphocyte (HTL) epitope which binds an HLA class 11 molecule in a human to elicit an HTL response. The peptides of the invention may be on the same or on one or more separate polypeptide molecules. In a further aspect of the invention, the agent comprises one or more than one nucleic acid molecule that expresses one or more than one of the CTL or HTL response stimulating peptides as described above. In yet another aspect of the invention, the one or more than one nucleic acid molecule may express a moiety that is immunologically reactive with 109P1 D4 as described above. The one or more than one nucleic acid molecule may also be, or encodes, a molecule that inhibits production of 109P1 D4. Non-limiting examples of such molecules include, but are not limited to, those complementary to a nucleotide sequence essential for production of 109P1 D4 (e. g. antisense sequences or molecules that form a triple helix with a nucleotide double helix essential for 109P1 D4 production) or a ribozyme effective to lyse 109P1 D4 mRNA.

Note that to determine the starting position of any peptide set forth in Tables VIII-XXI and XXII to XLIX (collectively HLA Peptide Tables) respective to its parental protein, e. g., variant 1, variant 2, etc., reference is made to three factors : the particular variant, the length of the peptide in an HLA Peptide Table, and the Search Peptides in Table VII. Generally, a unique Search Peptide is used to obtain HLA peptides of a particular for a particular variant. The position of each Search Peptide relative to its respective parent molecule is listed in Table Vil. Accordingly, if a Search Peptide begins at position "X", one must add the value"X-1"to each position in Tables VIII-XXI and XXII to XLIX to obtain the actual position of the HLA peptides in their parental molecule. For example, if a particular Search Peptide begins at position 150 of its parental molecule, one must add 150-1, i. e., 149 to each HLA peptide amino acid position to calculate the position of that amino acid in the parent molecule.

One embodiment of the invention comprises an HLA peptide, that occurs at least twice in Tables VIII-XXI and XXII to XLIX collectively, or an oligonucleotide that encodes the HLA peptide. Another embodiment of the invention comprises an HLA peptide that occurs at least once in Tables VIII-XXI and at least once in tables XXII to XLIX, or an oligonucleotide that encodes the HLA peptide.

Another embodiment of the invention is antibody epitopes, which comprise a peptide regions, or an oligonucleotide encoding the peptide region, that has one two, three, four, or five of the following characteristics : i) a peptide region of at least 5 amino acids of a particular peptide of Figure 3, in any whole number increment up to the full length of that protein in Figure 3, that includes an amino acid position having a value equal to or greater than 0. 5, 0. 6, 0. 7, 0. 8, 0. 9, or having a value equal to 1. 0, in the Hydrophilicity profile of Figure 5 ; ii) a peptide region of at least 5 amino acids of a particular peptide of Figure 3, in any whole number increment up to the full length of that protein in Figure 3, that includes an amino acid position having a value equal to or less than 0. 5, 0. 4, 0. 3, 0. 2, 0. 1, or having a value equal to 0. 0, in the Hydropathicity profile of Figure 6 ; iii) a peptide region of at least 5 amino acids of a particular peptide of Figure 3, in any whole number increment up to the full length of that protein in Figure 3, that includes an amino acid position having a value equal to or greater than 0. 5, 0. 6, 0. 7, 0. 8, 0. 9, or having a value equal to 1. 0, in the Percent Accessible Residues profile of Figure 7 ; iv) a peptide region of at least 5 amino acids of a particular peptide of Figure 3, in any whole number increment up to the full length of that protein in Figure 3, that includes an amino acid position having a value equal to or greater than 0. 5, 0. 6, 0. 7, 0. 8, 0. 9, or having a value equal to 1. 0, in the Average Flexibility profile of Figure 8 ; or v) a peptide region of at least 5 amino acids of a particular peptide of Figure 3, in any whole number increment up to the full length of that protein in Figure 3, that includes an amino acid position having a value equal to or greater than 0. 5, 0. 6, 0. 7, 0. 8, 0. 9, or having a value equal to 1. 0, in the Beta-turn profile of Figure 9.

BRIEF DESCRIPTION OF THE FIGURES Figure 1. The 109P1 D4 SSH sequence of 192 nucleotides.

Figure 2. A) The cDNA and amino acid sequence of109P1D4variant1 (also ca ! ied"109P1D4 v. 1"or"109P1D4 variant 1") is shown in Figure 2A, The start methionine is underlined. The open reading frame extends from nucleic acid 846-3911 including the stop codon.

B) The cDNA and amino acid sequence of 109P1D4 variant 2 (also called"1 09P1 D4 v. 2") is shown in Figure 2B.

The codon for the start methionine is underlined. The open reading frame extends from nucleic acid 503-3667 including the stop codon.

C) The cDNA and amino acid sequence of 109P1 D4 variant 3 (also called"109P1 D4 v. 3") is shown in Figure 2C.

The codon for the start methionine is underlined. The open reading frame extends from nucleic acid 846-4889 including the stop codon.

D) The cDNA and amino acid sequence of 109P1D4 variant 4 (also called"1 09P1 D4 v. 4") is shown in Figure 2D.

The codon for the start methionine is underlined. The open reading frame extends from nucleic acid 846-4859 including the stop codon.

E) The cDNA and amino acid sequence of 109P1D4 variant 5 (also called"1 09P1 D4 v. 5") is shown in Figure 2E.

The codon for the start methionine is underlined. The open reading frame extends from nucleic acid 846-4778 including the stop codon.

F) The cDNA and amino acid sequence of 109P1D4 variant 6 (also called"1 09P1 D4 v. 6") is shown in Figure 2F.

The codon for the start methionine is underlined. The open reading frame extends from nucleic acid 614-3727 including the stop codon.

G) The cDNA and amino acid sequence of 109P1D4 variant 7 (also called"1 09P1 D4 v. 7") is shown in Figure 2G.

The codon for the start methionine is underlined. The open reading frame extends from nucleic acid 735-3881 including the stop codon.

H) The cDNA and amino acid sequence of 109P1D4 variant 8 (also called"109P1D4 v. 8") is shown in Figure 2H.

The codon for the start methionine is underlined. The open reading frame extends from nucleic acid 735-4757 including the stop codon.

I) The cDNA and amino acid sequence of 109P1 D4 variant 9 (also called"1 09P1 D4 v. 9") is shown in Figure 21.

The codon for the start methionine is underlined. The open reading frame extends from nucleic acid 514-3627 including the stop codon.

J) 109P1 D4 v. 1, v. 2 and v. 3 SNP variants. Though these SNP variants are shown separately, they can also occur in any combinations and in any of the transcript variants listed above.

K) 109P1 D4 v. 6, v. 7 and v. 8 SNP variants. Though these SNP variants are shown separately, they can also occur in at combinations and in any of the transcript variants listed above.

Figure 3.

A) The amino acid sequence of 109P1D4 v. 1 is shown in Figure 3A ; it has 1021 amino acids.

B) The amino acid sequence of 109P1D4 v. 2 is shown in Figure 3B ; it has 1054 amino acids.

C) The amino acid sequence of 109P1D4 v. 3 is shown in Figure 3C ; it has 1347 amino acids.

D) The amino acid sequence of 109P1D4 v. 4 is shown in Figure 3D ; it has 1337 amino acids.

E) The amino acid sequence of 109P1D4 v. 5 is shown in Figure 3E ; it has 1310 amino acids.

F) The amino acid sequence of 109P1D4 v. 6 is shown in Figure 3F ; it has 1037 amino acids.

G) The amino acid sequence of 109P1D4 v. 7 is shown in Figure 3G ; it has 1048 amino acids.

H) The amino acid sequence of 109P1 D4 v. 8 is shown in Figure 3H ; it has 1340 amino acids.

I) The amino acid sequence of 109P1D4 v. 9 is shown in Figure 31 ; it has 1037 amino acids.

As used herein, a reference to 109P1D4 includes all variants thereof, including those shown in Figures 2, 3, 10, 11, and 12 unless the context clearly indicates otherwise.

Figure 4. Alignment of 109P1 D4 v. 1 Protein with protocadherin-11., Figure 5. Hydrophilicity amino acid profile of 109P1D4 v. 1-v. 9 determined by computer algorithm sequence analysis using the method of Hopp and Woods (Hopp T. P., Woods K. R., 1981. Proc. Natl. Acad. Sci. U. S. A. 78 : 3824-3828) accessed on the Protscale website located on the World Wide Web at (expasy. ch/cgi-bin/protscale. pl) through the ExPasy molecular biology server.

Figure 6. Hydropathicity amino acid profile of 109P1D4 v. 1-v. 9 determined by computer algorithm sequence analysis using the method of Kyte and Doolittle (Kyte J., Doolittle R. F., 1982. J. Mol. Biol. 157 : 105-132) accessed on the ProtScale website located on the World Wide Web at (. expasy. ch/cgi-bin/protscale. pl) through the ExPasy molecular biology server.

Figure 7. Percent accessible residues amino acid profile of 109P1 D4 v. 1-v. 9 determined by computer algorithm sequence analysis using the method of Janin (Janin J., 1979 Nature 277 : 491-492) accessed on the ProtScale website located on the World Wide Web at (. expasy. ch/cgi-bin/protscale. pl) through the ExPasy molecular biology server.

Figure 8. Average flexibility amino acid profile of 109P1 D4 v. 1-v. 9 determined by computer algorithm sequence analysis using the method of Bhaskaran and Ponnuswamy (Bhaskaran R., and Ponnuswamy P. K., 1988. Int. J. Pept. Protein Res. 32 : 242-255) accessed on the ProtScale website located on the World Wide Web at (. expasy. ch/cgi-bin/protscale. pl) through the ExPasy molecular biology server.

Figure 9. Beta-turn amino acid profile of 109P1 D4 v. 1-v. 9 determined by computer algorithm sequence analysis using the method of Deleage and Roux (Deleage, G., Roux B. 1987 Protein Engineering 1 : 289-294) accessed on the ProtScale website located on the World Wide Web at (. expasy. ch/cgi-bin/protscale. pl) through the ExPasy molecular biology server.

Figure 10. Structure of transcript variants of 109P1D4. Variants 109P1D4 v. 2 through v. 9 were transcript variants of v. 1. Variant v. 2 shared middle portion of v. 1 sequence (the 3'portion of exon 1 and 5'portion of exon 2). Variant v. 6 was similar to v. 2 but added an extra exon between exons 1 and 2 of v. 2. V. 3 shared exon 1 and 5'portion of exon 2 with v. 1 with five additional exons downstream. Compared with v. 3, v. 4 deleted exon 4 of v. 3 while v. 5 deleted exons 3 and 4 of v. 3. Variant v. 5 lacked exons 3 and 4. This gene (called PCD11) is located in sex chromosomes X and Y. Ends of exons in the transcripts are marked above the boxes. Potential exons of this gene are shown in order as on the human genome. Poly A tails and single nucleotide differences are not shown in the figure. Lengths of introns and exons are not proportional.

Figure It Schematic alignment of protein variants of 109P1D4. Variants 109P1D4 v. 2 through v. 9 were proteins translated from the corresponding transcript variants. All these protein variants shared a common portion of the sequence, i. e., 3-1011 of v. 1, except for a few amino acids different in this segment resulted from SNP in the transcripts.

Variant v. 6 and v. 9 were the same except for two amino acids at 906 and 1001. Variant v. 8 was almost the same as v. 5, except for the N-terminal end, and a 2-aa deletion at 1117-8. Single amino acid difference was not shown. Numbers in parentheses corresponded to positions in variant v. 3.

Figure 12. Intentionally Omitted.

Figure 13. Figures 13 (a)- (i) : Secondary structure and transmembrane domains prediction for 109P1 D4 protein variants 1-9 (v. 1- (SEQ ID NO : 31) ; v. 2- (SEQ ID NO : 32) ; v. 3- (SEQ ID NO : 33) ; v. 4- (SEQ ID NO : 34) ; v. 5- (SEQ ID NO : 35) ; v. 6- (SEQ ID NO : 36) ; vi7- (SEQ ID NO : 37) ; v. 8- (SEQ ID NO : 38) ; v. 9- (SEQ ID NO : 39)). The secondary structures of 109P1 D4 protein variants were predicted using the HNN-Hierarchical Neural Network method (NPS@ : Network Protein Sequence Analysis TIBS 2000 March Vol. 25, No 3 [291] : 147-150 Combet C., Blanchet C., Geourjon C. and Deléage G., http ://pbil. ibCp. fr/cgi-bin/npsa_automat. plvpage=npsa_nn. html), accessed from the ExPasy molecular biology server located on the World Wide Web at (. expasy. ch/tools/). This method predicts the presence and location of alpha helices, extended strands, and random coils from the primary protein sequence. The percent of the protein variant in a given secondary structure is also listed. Figures 13 (J)- (R) top panels : Schematic representation of the probability of existence of transmembrane regions of 109P1 D4 variants based on the TMpred algorithm of Hofmann and Stoffel which utilizes TMBASE (K. Hofmann, W. Stoffe. TMBASE-A database of membrane spanning protein segments Biol. Chem. Hoppe-Seyler 374 : 166, 1993). Figures 13 (J)- (R) bottom panels : Schematic representation of the probability of the existence of transmembrane regions of 109P1D4 variants based on the TMHMM algorithm of Sonnhammer, von Heijne, and Krogh (Erik L. L. Sonnhammer, Gunnar von Heijne, and Anders Krogh : A hidden Markov model for predicting transmembrane helices in protein sequences. In Proc. of Sixth Int. Conf. on Intelligent Systems for Molecular Biology, p 175-182 Ed J. Glasgow, T.

Littlejohn, F. Major, R. Lathrop, D. Sankoff, and C. Sensen Menlo Park, CA : AAAI Press, 1998). The TMpred and TMHMM algorithms are accessed from the ExPasy molecular biology server located on the World Wide Web at (. expasy. ch/tools/).

Figure 14. Expression of 109P1D4 in Lymphoma Cancer Patient Specimens. RNA was extracted from peripheral blood lymphocytes, cord blood isolated from normal individuals, and from lymphoma patient cancer specimens.

Northern blots with 1 Opg of total RNA were probed with the 109P1 D4 sequence. Size standards in kilobases are on the side. Results show expression of 109P1 D4 in lymphoma patient specimens but not in the normal blood cells tested.

Figure 15. Expression of 109P1D4 by RT-PCR. First strand cDNA was prepared from vital pool 1 (liver, lung and kidney), vital pool 2 (pancreas, colon and stomach), prostate cancer pool, bladder cancer pool, kidney cancer pool, colon cancer pool, lung cancer pool, ovary cancer pool, breast cancer pool, cancer metastasis pool, and pancreas cancer pool. Normalization was performed by PCR using primers to actin and GAPDH. Semi-quantitative PCR, using primers to 109P1 D4, was performed at 30 cycles of amplification. Results show strong expression of 109P1 D4 in all cancer pools tested. Very low expression was detected in the vital pools.

Figure 16. Expression of 109P1D4 in normal tissues. Two multiple tissue northern blots (Clontech), both with 2 ag of mRNAllane, were probed with the 109P1 D4 SSH fragment. Size standards in kilobases (kb) are indicated on the side.

Results show expression of approximately 10 kb 109P1D4 transcript in ovary. Weak expression was also detected in placenta and brain, but not in the other normal tissues tested.

Figure 17. Expression of 109P1D4 in human cancer cell lines. RNA was extracted from a number of human prostate and bone cancer cell lines. Northern blots with 10 ug of total RNAllane were probed with the 109P1 D4 SSH fragment. Size standards in kilobases (kb) are indicated on the side. Results show expression of 109P1 D4 in LAPC-9AD, LAPC-9AI, LNCaP prostate cancer cell lines, and in the bone cancer cell lines, SK-ES-1 and RD-ES.

Figure 18. Figure 18A : 09PI D4 Expression in Human Normal Tissues. An cDNA dot blot containing 76 different samples from human tissues was analyzed using a 109P1D4 SSH probe. Expression was only detected in multiple areas of the brain, placenta, ovary, and fetal brain, amongst all tissues tested. Figure 18B : Expression of 109P1D4 in patient cancer specimens. Expression of 109P1 D4 was assayed in a panel of human cancers (T) and their respective matched normal tissues (N) on RNA dot blots. Upregulated expression of 109P1 D4 in tumors compared to normal tissues was observed in uterus, lung and stomach. The expression detected in normal adjacent tissues (isolated from diseased tissues) but not in normal tissues (isolated from healthy donors) may indicate that these tissues are not fully normal and that 109P1 D4 may be expressed in early stage tumors.

Figure 19. 109P1 D4 Expression in Lung Cancer Patient Specimens. RNA was extracted from normal lung, prostate cancer xenograft LAPC-9AD, bone cancer cell line RD-ES, and lung cancer patient tumors. Northern blots with 10 tjg of total RNA were probed with 109P1 D4. Size standards in kilobases are on the side. Results show strong expression of 109P1 D4 in lung tumor tissues as well as the RD-ES cell line, but not in normal lung.

Figure 20. Expression of soluble secreted Tag5109P1 D4 in 293T cells. 293T cells were transfected with either an empty vector or with the Tag5 secretion vector encoding the extracellular domain (ECD ; amino acids 24-812) of 109P1 D4 variant 1 fused to a Myc/His epitope Tag. 2 days later, cells and media harvested and analyzed for expression of the recombinant Tag5 109P1 D4 protein by SDS-PAGE followed by anti-His epitope tag Western blotting. An arrow indicates the immunoreactive band corresponding to the 109P1D4 ECD present in the media and the lysate from Tag5 109PI D4 transfected cells.

Figure 21. Expression of 109P1 D4 protein in 293T cells. 293T cells were transfected with either an empty vector or with pCDNA3. 1 vector encoding the full length cDNA of 109P1 D4 variant 1 fused to a Myc/His epitope Tag. 2 days later, cells were harvested and analyzed for expression of 109P1D4 variant 1 protein by SDS-PAGE followed by anti-His epitope tag Western blotting. An arrow indicates the immunoreactive band corresponding to the full length 109P1 D4 variant 1 protein expressed in cells transfected with the 109P1 D4 vector but not in control cells.

Figure 22. Tyrosine phosphorylation of 109P1 D4 after pervanadate treatment. 293T cells were transfected with the neomycin resistance gene alone or with 109P1 D4 in pSRp vector. Twenty four hours after transfection, the cells were either left in 10% serum or grown in 0. 1 % serum overnight. The cells were then left untreated or were treated with 200 pM pervanadate (1 : 1 mixture of Na3V04 and H202) for 30 minutes. The cells were lysed in Triton X-100, and the 109P1 D4 protein was immunoprecipitated with anti-His monoclonal antibody. The immunoprecipitates were run on SDS-PAGE and then Western blotted with either anti-phosphotyrosine (upper panel) or anti-His (lower panel). The 109PI D4 protein is phosphorylated on tyrosine in response to pervanadate treatment, and a large amount of the protein moves to the insoluble fraction following pervanadate-induced activation.

Figure 23. Effect of 109P1 D4 RNAi on cell proliferation. LNCaP cells were transfected with Lipofectamine 2000 alone or with siRNA oligonucleotides. The siRNA oligonucleotides included a negative control, Luc4, specific for Luciferase, a positive control, Eg5, specific for the mitotic spindle protein Eg5, or three siRNAs specific for the 109P1 D4 protein, 109P1 D4. a, 109P1 D4. c and 109P1 D4. d at 20 nM concentration. Twenty four hours after transfection, the cells were pulsed with 3H-thymidine and incorporation was measured after 72 hours. All three siRNAs to 109P1 D4 inhibited the proliferation of LNCaP cells, indicating that 109P1 D4 expression is important for the cell growth pathway of these cancer cells.

DETAILED DESCRIPTION OF THE INVENTION Outline of Sections 1.) Definitions II.) 109P1D4 Polynucleotides II. A.) Uses of 109P1D4 Polynucleotides II. A. 1.) Monitoring of Genetic Abnormaliiies II. A. 2.) Antisense Embodiments II. 23.) Primers and Primer Pairs II. A. 4.) Isolation of 109P1D4-Encoding Nucleic Acid Molecules II. A. 5.) Recombinant Nucleic Acid Molecules and Host-Vector Systems III.) 109P1D4-related Proteins III. A.) Motif-bearing Protein Embodiments III. B.) Expression of 109P1D4-related Proteins III. C.) Modifications of 109P1D4-related Proteins III. D.) Uses of 109P1D4-related Proteins IV.) 109P1D4 Antibodies V.) 109P1 D4 Cellular Immune Responses VI.) 109P1D4 Transgenic Animals VII.) Methods for the Detection of 109P1 D4 VIII.) Methods for Monitoring the Status of 109P1 D4-related Genes and Their Products IX.) Identification of Molecules That Interact With 109P1D4 X.) Therapeutic Methods and Compositions X. A.) Anti-Cancer Vaccines X. B.) 109P1 D4 as a Target for Antibody-Based Therapy X.C.) 109P1D4 as a Target for Cellular Immune Responses X. C. 1. Minigene Vaccines X. C. 2. Combinations of CTL Peptides with Helper Peptides X. C. 3. Combinations of CTL Peptides with T Cell Priming Agents X. C. 4. Vaccine Compositions Comprising DC Pulsed with CTL and/or HTL Peptides X. D.) Adoptive immunotherapy X. E.) Administration of Vaccines for Therapeutic or Prophylactic Purposes Xi.) Diagnostic and Prognostic Embodiments of 109P1D4.

Xil.) Inhibition of 109P1D4 Protein Function XII. A.) Inhibition of 109P1D4 With Intracellular Antibodies XII. B.) Inhibition of 109P1D4 with Recombinant Proteins XII. C.) Inhibition of 109P1 D4 Transcription or Translation XII. D.) General Considerations for Therapeutic Strategies XIII.) Identifications, Characterization and Use of Modulators of 109P1 D4 XIV.) KITSIArticles of Manufacture (.)-Definitions- Unless otherwise defined, all terms of art, notations and other scientific terms or terminology used herein are intended to have the meanings commonly understood by those of skill in the art to which this invention pertains. In some cases, terms with commonly understood meanings are defined herein for clarity andlor for ready reference, and the inclusion of such definitions herein should not necessarily be construed to represent a substantial difference over what is generally understood in the art. Many of the techniques and procedures described or referenced herein are well understood and commonly employed using conventional methodology by those skilled in the art, such as, for example, the widely utilized molecular cloning methodologies described in Sambrook et al., Molecular Cloning : A Laboratory Manual 2nd. edition (1989) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N. Y. As appropriate, procedures involving the use of commercially available kits and reagents are generally carried out in accordance with manufacturer defined protocols and/or parameters unless otherwise noted.

The terms"advanced prostate cancer","locally advanced prostate cancer","advanced disease"and"locally advanced disease"mean prostate cancers that have extended through the prostate capsule, and are meant to include stage C disease under the American Urological Association (AUA) system, stage C1-C2 disease under the Whitmore-Jewett system, and stage T3-T4 and N+ disease under the TNM (tumor, node, metastasis) system. In general, surgery is not recommended for patients with locally advanced disease, and these patients have substantially less favorable outcomes compared to patients having clinically localized (organ-confined) prostate cancer. Locally advanced disease is clinically identified by palpable evidence of induration beyond the lateral border of the prostate, or asymmetry or induration above the prostate base. Locally advanced prostate cancer is presently diagnosed pathologically following radical prostatectomy if the tumor invades or penetrates the prostatic capsule, extends into the surgical margin, or invades the seminal vesicles.

"Altering the native glycosylation pattern"is intended for purposes herein to mean deleting one or more carbohydrate moieties found in native sequence 109P1 D4 (either by removing the underlying glycosylation site or by deleting the glycosylation by chemical and/or enzymatic means), and/or adding one or more glycosylation sites that are not present in the native sequence 109P1 D4. In addition, the phrase includes qualitative changes in the glycosylation of the native proteins, involving a change in the nature and proportions of the various carbohydrate moieties present.

The term"analog"refers to a molecule which is structurally similar or shares similar or corresponding attributes with another molecule (e. g. a 109P1 D4-reiated protein). For example, an analog of a 109P1D4 protein can be specifically bound by an antibody or T cell that specifically binds to 109P1 D4.

The term"antibody"is used in the broadest sense. Therefore, an"antibody"can be naturally occurring or man-made such as monoclonal antibodies produced by conventional hybridoma technology. Anti-109P1D4 antibodies comprise monoclonal and polyclonal antibodies as well as fragments containing the antigen-binding domain andlor one or more complementarity determining regions of these antibodies.

An"antibody fragment"is defined as at least a portion of the variable region of the immunoglobulin molecule that binds to its target, i. e., the antigen-binding region. In one embodimentitspecifically covers single anti-109P1D4 antibodies and clones thereof (including agonist, antagonist and neutralizing antibodies) and anti-109P1 D4 antibody compositions with polyepitopic specificity.

The term"codon optimized sequences"refers to nucleotide sequences that have been optimized for a particular host species by replacing any codons having a usage frequency of less than about 20%. Nucleotide sequences that have been optimized for expression in a given host species by elimination of spurious polyadenylation sequences, elimination of exonlintron splicing signals, elimination of tansposon-like repeats and/or optimization of GC content in addition to codon optimization are referred to herein as an"expression enhanced sequences." A"combinatorial library"is a collection of diverse chemical compounds generated by either chemical synthesis or biological synthesis by combining a number of chemical"building blocks"such as reagents. For example, a linear combinatorial chemical library, such as a polypeptide (e. g., mutein) library, is formed by combining a set of chemical building blocks called amino acids in every possible way for a given compound length (i. e., the number of amino acids in a polypeptide compound). Numerous chemical compounds are synthesized through such combinatorial mixing of chemical building blocks (Gallop et al., J. Med. Chem. 37 (9) : 1233-1251 (1994)).

Preparation and screening of combinatorial libraries is well known to those of skill in the art. Such combinatorial chemical libraries include, but are not limited to, peptide libraries (see, e. g., U. S. Patent No. 5, 010, 175, Furka, Pept. Prot.

Res. 37 : 487-493 (1991), Houghton et al., Nature, 354 : 84-88 (1991)), peptoids (PCT Publication No WO 91/19735), encoded peptides (PCT Publication WO 93/20242), random bio-oligomers (PCT Publication WO 92/00091), benzodiazepines (U. S.

Pat. No. 5, 288, 514), diversomers such as hydantoins, benzodiazepines and dipeptides (Hobbs et al., Proc. Nat. Acad. Sci.

USA 90 : 6909-6913 (1993)), vinylogous polypeptides (Hagihara et al., J. Amer. Chem. Soc. 114 : 6568 (1992)), nonpeptidal peptidomimetics with a Beta-D-Glucose scaffolding (Hirschmann et al., J. Amer. Chem. Soc. 114 : 9217-9218 (1992)), analogous organic syntheses of small compound libraries (Chen et al., J. Amer. Chem. Soc. 116 : 2661 (1994)), oligocarbarnates (Cho, et al., Science 261 : 1303 (1993)), and/or peptidyl phosphonates (Campbell et al., J. Org. Chem.

59 : 658 (1994)). See, generally, Gordon et al., J. Med. Chem. 37 : 1385 (1994), nucleic acid libraries (see, e. g., Stratagene, Corp.), peptide nucleic acid libraries (see, e. g., U. S. Patent 5, 539, 083), antibody libraries (see, e. g., Vaughn et al., Nature Biotechnology 14 (3) : 309-314 (1996), and PCT/US96/10287), carbohydrate libraries (see, e. g., Liang et al., Science 274 : 1520-1522 (1996), and U. S. Patent No. 5, 593, 853), and small organic molecule libraries (see, e. g., benzodiazepines, Baum, C&EN, Jan 18, page 33 (1993) ; isoprenoids, U. S. Patent No. 5, 569, 588 ; thiazolidinones and metathiazanones, U. S.

Patent No. 5, 549, 974 ; pyrrolidines, U. S. Patent Nos. 5, 525, 735 and 5, 519, 134 ; morpholino compounds, U. S. Patent No.

5, 506, 337 ; benzodiazepines, U. S. Patent No. 5, 288, 514 ; and the like).

Devices for the preparation of combinatorial libraries are commercially available (see, e. g., 357 NIPS, 390 NIPS, Advanced Chem Tech, Louisville KY ; Symphony, Rainin, Woburn, MA ; 433A, Applied Biosystems, Foster City, CA ; 9050, Plus, Millipore, Bedford, NIA). A number of well-known robotic systems have also been developed for solution phase chemistries. These systems include automated workstations such as the automated synthesis apparatus developed by Takeda Chemical Industries, LTD. (Osaka, Japan) and many robotic systems utilizing robotic arms (Zymate H, Zymark Corporation, Hopkinton, Mass. ; Orca, Hewlett-Packard, Palo Alto, Calif.), which mimic the manual synthetic operations performed by a chemist. Any of the above devices are suitable for use with the present invention. The nature and implementation of modifications to these devices (if any) so that they can operate as discussed herein will be apparent to persons skilled in the relevant art. In addition, numerous combinatorial libraries are themselves commercially available (see, e. g., ComGenex, Princeton, NJ ; Asinex, Moscow, RU ; Tripos, Inc., St. Louis, MO ; ChemStar, Ltd, Moscow, RU ; 3D Pharmaceuticals, Exton, PA ; Martek Biosciences, Columbia, MD ; etc.).

The term"cytotoxic agent"refers to a substance that inhibits or prevents the expression activity of cells, function of cells and/or causes destruction of cells. The term is intended to include radioactive isotopes chemotherapeutic agents, and toxins such as small molecule toxins or enzymatically active toxins of bacterial, fungal, plant or animal origin, including fragments and/or variants thereof. Examples of cytotoxic agents include, but are not limited to auristatins, auromycins, maytansinoids, yttrium, bismuth, ricin, ricin A-chain, combrestatin, duocarmycins, dolostatins, doxorubicin, daunorubicin, taxol, cisplatin, cc1065, ethidium bromide, mitomycin, etoposide, tenoposide, vincristine, vinblastine, colchicine, dihydroxy anthracin dione, actinomycin, diphtheria toxin, Pseudomonas exotoxin (PE) A, PE40, abrin, abrin A chain, modeccin A chain, alpha-sarcin, gelonin, mitogellin, retstrictocin, phenomycin, enomycin, curicin, crotin, calicheamicin, Sapaonaria offcinalis inhibitor, and glucocorticoid and other chemotherapeutic agents, as well as radioisotopes such as At211, j131, is yso, Repas Re188, Sm153, Bj2120r213, psz and radioactive isotopes of Lu including Lul77. Antibodies may also be conjugated to an anti- cancer pro-drug activating enzyme capable of converting the pro-drug to its active form.

The"gene products sometimes referred to herein as a protein or mRNA. For example, a"gene product of the invention"is sometimes referred to herein as a"cancer amino acid sequence","cancer protein","protein of a cancer listed in Table I", a"cancer mRNA","mRNA of a cancer listed in Table I", etc. In one embodiment, the cancer protein is encoded by a nucleic acid of Figure 2. The cancer protein can be a fragment, or alternatively, be the full-length protein to the fragment encoded by the nucleic acids of Figure 2. In one embodiment, a cancer amino acid sequence is used to determine sequence identity or similarity. In another embodiment, the sequences are naturally occurring allelic variants of a protein encoded by a nucleic acid of Figure 2. In another embodiment, the sequences are sequence variants as further described herein.

"High throughput screening"assays for the presence, absence, quantification, or other properties of particular nucleic acids or protein products are well known to those of skill in the art. Similarly, binding assays and reporter gene assays are similarly well known. Thus, e. g., U. S. Patent No. 5, 559, 410 discloses high throughput screening methods for proteins ; U. S. Patent No. 5, 585, 639 discloses high throughput screening methods for nucleic acid binding (i. e., in arrays) ; while U. S. Patent Nos. 5, 576, 220 and 5, 541, 061 disclose high throughput methods of screening for ligand/antibody binding.

In addition, high throughput screening systems are commercially available (see, e. g., Amersham Biosciences, Piscataway, NJ ; Zymark Corp., Hopkinton, MA ; Air Technical Industries, Mentor, OH ; Beckman Instruments, Inc. Fullerton, CA ; Precision Systems, Inc., Natick, MA ; etc.). These systems typically automate entire procedures, including all sample and reagent pipetting, liquid dispensing, timed incubations, and final readings of the microplate in detector (s) appropriate for the assay. These configurable systems provide high throughput and rapid start up as well as a high degree of flexibility and customization. The manufacturers of such systems provide detailed protocols for various high throughput systems. Thus, e. g., Zymark Corp. provides technical bulletins describing screening systems for detecting the modulation of gene transcription, ligand binding, and the like.

The term"homolog"refers to a molecule which exhibits homology to another molecule, by for example, having sequences of chemical residues that are the same or similar at corresponding positions.

"Human Leukocyte Antigen"or"HLA"is a human class I or class 11 Major Histocompatibility Complex (MHC) protein (see, e. g., Stites, et al., IMMUNOLOGY, 8TH ED., Lange Publishing, Los Altos, CA (1994).

The terms"hybridize","hybridizing","hybridizes"and the like, used in the context of polynucleotides, are meant to refer to conventional hybridization conditions, preferably such as hybridization in 50% formamide/6XSSC/0. 1 % SDS/100 lig/ml ssDNA, in which temperatures for hybridization are above 37 degrees C and temperatures for washing in 0. 1XSSC/0. 1% SDS are above 55 degrees C.

The phrases"isolated"or"biologically pure"refer to material which is substantially or essentially free from components which normally accompany the material as it is found in its native state. Thus, isolated peptides in accordance with the invention preferably do not contain materials normally associated with the peptides in their in situ environment. For example, a polynucleotide is said to be"isolated"when it is substantially separated from contaminant polynucleotides that correspond or are complementary to genes other than the 109P1 D4 genes or that encode polypeptides other than 109P1 D4 gene product or fragments thereof. A skilled artisan can readily employ nucleic acid isolation procedures to obtain an isolated 109P1 D4 polynucleotide. A protein is said to be"isolated,"for example, when physical, mechanical or chemical methods are employed to remove the 109P1D4 proteins from cellular constituents that are normally associated with the protein. A skilled artisan can readily employ standard purification methods to obtain an isolated 109P1 D4 protein. Alternatively, an isolated protein can be prepared by chemical means.

The term"mammal"refers to any organism classified as a mammal, including mice, rats, rabbits, dogs, cats, cows, horses and humans. In one embodiment of the invention, the mammal is a mouse. In another embodiment of the invention, the mammal is a human.

The terms"metastatic prostate cancer"and"metastatic disease"mean prostate cancers that have spread to regional lymph nodes or to distant sites, and are meant to include stage D disease under the AUA system and stage TxNxM+ under the TNM system. As is the case with locally advanced prostate cancer, surgery is generally not indicated for patients with metastatic disease, and hormonal (androgen ablation) therapy is a preferred treatment modality. Patients with metastatic prostate cancer eventually develop an androgen-refractory state within 12 to 18 months of treatment initiation.

Approximately half of these androgen-refractory patients die within 6 months after developing that status. The most common site for prostate cancer metastasis is bone. Prostate cancer bone metastases are often osteoblastic rather than osteolytic (i. e., resulting in net bone formation). Bone metastases are found most frequently in the spine, followed by the femur, pelvis, rib cage, skull and humerus. Other common sites for metastasis include lymph nodes, lung, liver and brain. Metastatic prostate cancer is typically diagnosed by open or laparoscopic pelvic lymphadenectomy, whole body radionuclide scans, skeletal radiography, and/or bone lesion biopsy.

The term"modulator"or"test compound"or"drug candidate"or grammatical equivalents as used herein describe any molecule, e. g., protein, oligopeptide, small organic molecule, polysaccharide, polynucleotide, etc., to be tested for the capacity to directly or indirectly alter the cancer phenotype or the expression of a cancer sequence, e. g., a nucleic acid or protein sequences, or effects of cancer sequences (e. g., signaling, gene expression, protein interaction, etc.) In one aspect, a modulator will neutralize the effect of a cancer protein of the invention. By"neutralize"is meant that an activity of a protein is inhibited or blocked, along with the consequent effect on the cell. In another aspect, a modulator will neutralize the effect of a gene, and its corresponding protein, of the invention by normalizing levels of said protein. In preferred embodiments, modulators alter expression profiles, or expression profile nucleic acids or proteins provided herein, or downstream effector pathways. In one embodiment, the modulator suppresses a cancer phenotype, e. g. to a normal tissue fingerprint. In another embodiment, a modulator induced a cancer phenotype. Generally, a plurality of assay mixtures is run in parallel with different agent concentrations to obtain a differential response to the various concentrations. Typically, one of these concentrations serves as a negative control, i. e., at zero concentration or below the level of detection.

Modulators, drug candidates or test compounds encompass numerous chemical classes, though typically they are organic molecules, preferably small organic compounds having a molecular weight of more than 100 and less than about 2, 500 Daltons. Preferred small molecules are less than 2000, or less than 1500 or less than 1000 or less than 500 D.

Candidate agents comprise functional groups necessary for structural interaction with proteins, particularly hydrogen bonding, and typically include at least an amine, carbonyl, hydroxyl or carboxyl group, preferably at least two of the functional chemical groups. The candidate agents often comprise cyclical carbon or heterocyclic structures and/or aromatic or polyaromatic structures substituted with one or more of the above functional groups. Modulators also comprise biomolecules such as peptides, saccharides, fatty acids, steroids, purines, pyrimidines, derivatives, structural analogs or combinations thereof. Particularly preferred are peptides. One class of modulators are peptides, for example of from about five to about 35 amino acids, with from about five to about 20 amino acids being preferred, and from about 7 to about 15 being particularly preferred. Preferably, the cancer modulator protein is soluble, includes a non-transmembrane region, and/or, has an N- terminal Cys to aid in solubility. In one embodiment, the C-terminus of the fragment is kept as a free acid and the N-terminus is a free amine to aid in coupling, i. e., to cysteine. In one embodiment, a cancer protein of the invention is conjugated to an immunogenic agent as discussed herein. In one embodiment, the cancer protein is conjugated to BSA. The peptides of the invention, e. g., of preferred lengths, can be linked to each other or to other amino acids to create a longer peptide/protein.

The modulator peptides can be digests of naturally occurring proteins as is outlined above, random peptides, or"biased" random peptides. In a preferred embodiment, peptide/protein-based modulators are antibodies, and fragments thereof, as defined herein.

Modulators of cancer can also be nucleic acids. Nucleic acid modulating agents can be naturally occurring nucleic acids, random nucleic acids, or"biased"random nucleic acids. For example, digests of prokaryotic or eukaryotic genomes can be used in an approach analogous to that outlined above for proteins.

The term"monoclonal antibody"refers to an antibody obtained from a population of substantially homogeneous antibodies, i. e., the antibodies comprising the population are identical except for possible naturally occurring mutations that are present in minor amounts.

A"motif', as in biological motif of a 109P1 D4-related protein, refers to any pattern of amino acids forming part of the primary sequence of a protein, that is associated with a particular function (e. g. protein-protein interaction, protein-DNA interaction, etc) or modification (e. g. that is phosphorylated, glycosylated or amidated), or localization (e. g. secretory sequence, nuclear localization sequence, etc.) or a sequence that is correlated with being immunogenic, either humorally or cellularly. A motif can be either contiguous or capable of being aligned to certain positions that are generally correlated with a certain function or property. In the context of HLA motifs,"motif'refers to the pattern of residues in a peptide of defined length, usually a peptide of from about 8 to about 13 amino acids for a class I HLA motif and from about 6 to about 25 amino acids for a class 11 HLA motif, which is recognized by a particular HLA molecule. Peptide motifs for HLA binding are typically different for each protein encoded by each human HLA allele and differ in the pattern of the primary and secondary anchor residues.

A"pharmaceutical excipient"comprises a material such as an adjuvant, a carrier, pH-adjusting and buffering agents, tonicity adjusting agents, wetting agents, preservative, and the like.

"Pharmaceutically acceptable"refers to a non-toxic, inert, and/or composition that is physiologically compatible with humans or other mammals.

The term"polynucleotide"means a polymeric form of nucleotides of at least 10 bases or base pairs in length, either ribonucleotides or deoxynucleotides or a modified form of either type of nucleotide, and is meant to include single and double stranded forms of DNA and/or RNA. In the art, this term if often used interchangeably with"oligonucleotide". A polynucleotide can comprise a nucleotide sequence disclosed herein wherein thymidine (T), as shown for example in Figure 2, can also be uracil (U) ; this definition pertains to the differences between the chemical structures of DNA and RNA, in particular the observation that one of the four major bases in RNA is uracil (U) instead of thymidine (T).

The term"polypeptide"means a polymer of at least about 4, 5, 6, 7, or 8 amino acids. Throughout the specification, standard three letter or single letter designations for amino acids are used. In the art, this term is often used interchangeably with"peptide"or"protein".

An HLA"primary anchor residue"is an amino acid at a specific position along a peptide sequence which is understood to provide a contact point between the immunogenic peptide and the HLA molecule. One to three, usually two, primary anchor residues within a peptide of defined length generally defines a"motif'for an immunogenic peptide. These residues are understood to fit in close contact with peptide binding groove of an HLA molecule, with their side chains buried in specific pockets of the binding groove. In one embodiment, for example, the primary anchor residues for an HLA class I molecule are located at position 2 (from the amino terminal position) and at the carboxyl terminal position of a 8, 9, 10, 11, or 12 residue peptide epitope in accordance with the invention. Alternatively, in another embodiment, the primary anchor residues of a peptide binds an HLA class 11 molecule are spaced relative to each other, rather than to the termini of a peptide, where the peptide is generally of at least 9 amino acids in length. The primary anchor positions for each motif and supermotif are set forth in Table IV. For example, analog peptides can be created by altering the presence or absence of particular residues in the primary and/or secondary anchor positions shown in Table IV. Such analogs are used to modulate the binding affinity and/or population coverage of a peptide comprising a particular HLA motif or supermotif.

"Radioisotopes"include, but are not limited to the following (non-limiting exemplary uses are also set forth) : Examples of Medical Isotopes : Isotope Description of use Actinium-225 -..... r) on/Tkoon\ Actinium-225 See Thorium-229 (Th-229) (AC-225) Actinium-227 Parent of Radium-223 (Ra-223) which is an alpha emitter used to treat metastases in the skeleton (AC-227) resulting from cancer (i. e., breast and prostate cancers), and cancer radioimmunotherapy Bismuth-212 p......-. ooo/ThooQ Bismuth-212 See Thorium-228 (Th-228) (Bi-212) Bismuth-213 See Thorium-229 (Th-229) (Bi-213) Cadmium-109 Cancer detection (Cd-109) Cobalt-60 Radiation source for radiotherapy of cancer, for food irradiators, and for sterilization of medical (Co-60) supplies Copper-64 A positron emitter used for cancer therapy and SPECT imaging (Cu-64) Copper-67 Beta/gamma emitter used in cancer radioimmunotherapy and diagnostic studies (i. e., breast and (Cu-67) colon cancers, and Iymphoma} Dysprosium-166 Cancer radioimmunotherapy (Dy-166) Erbium-169 Rheumatoid arthritis treatment, particularly for the small joints associated with fingers and toes (Er-169) (Eu-152) Radiation source for food irradiation and for sterilization of medical supplies (Eu-152) Europium-154 Radiation source for food irradiation and for sterilization of medical supplies (Eu-154) Gadolinium-153 Osteoporosis detection and nuclear medical quality assurance devices (Gd-153) Gold-198 Implant and intracavity therapy of ovarian, prostate, and brain cancers (Au-198) Holmium-166 Multiple myeloma treatment in targeted skeletal therapy, cancer radioimmunotherapy, bone (Ho-166) marrow ablation, and rheumatoid arthritis treatment Osteoporosis detection, diagnostic imaging, tracer drugs, brain cancer treatment, radiolabeling, lodine-125 tumor imaging, mapping of receptors in the brain, interstitial radiation therapy, brachytherapy for (1-125) treatment of prostate cancer, determination of glomerular filtration rate (GFR), determination of plasma volume, detection of deep vein thrombosis of the legs Iodine-131 Thyroid function evaluation, thyroid disease detection, treatment of thyroid cancer as well as other (1-131) non-malignant thyroid diseases (i. e., Graves disease, goiters, and hyperthyroidism), treatment of leukemia, lymphoma, and other forms of cancer (e. g., breast cancer) using radioimmunotherapy Iridium-192 Brachytherapy, brain and spinal cord tumor treatment, treatment of blocked arteries (i. e., (Ir-192) arteriosclerosis and restenosis), and implants for breast and prostate tumors Lutetium-177 Cancer radioimmunotherapy and treatment of blocked arteries (i. e., arteriosclerosis and (Lu-177) restenosis) Parent of Technetium-99m (Tc-99m) which is used for imaging the brain, liver, lungs, heart, and Molybdenum-99 other organs. Currently, Tc-99m is the most widely used radioisotope used for diagnostic imaging (Mo-99) of various cancers and diseases involving the brain, heart, liver, lungs ; also used in detection of deep vein thrombosis of the legs Osmium-194 Cancer radioimmunotherapy (Os-194) (Pd-103) Prostate cancer treatment (Pd-103) Platinum-195m Studies on biodistribution and metabolism of cisplatin, a chemotherapeutic drug (Pt-195m) Polycythemia rubra vera (blood cell disease) and leukemia treatment, bone cancer Phosphorus-32 diagnosis/treatment ; colon, pancreatic, and liver cancer treatment ; radiolabeling nucleic acids for (P-32) in vitro research, diagnosis of superficial tumors, treatment of blocked arteries (i. e., arteriosclerosis and restenosis), and intracavity therapy Phosphorus-33 Leukemia treatment, bone disease diagnosis/treatment, radiolabeling, and treatment of blocked (P-33) arteries (i. e., arteriosclerosis and restenosis) (Ra-223) See Actinium-227 (Ac-227) (Ra-223) Rhenium-186 Bone cancer pain relief, rheumatoid arthritis treatment, and diagnosis and treatment of lymphoma (Re-186) and bone, breast, colon, and liver cancers using radioimmunotherapy Rhenium-188 Cancer diagnosis and treatment using radioimmunotherapy, bone cancer pain relief, treatment of (Re-188) rheumatoid arthritis, and treatment of prostate cancer Rhodium-105 Cancer radioimmunotherapy (Rh-105J Samarium-145 Ocular cancer treatment (Sm-145) Samarium-153 Cancer radioimmunotherapy and bone cancer pain relief (Sm-153) Scandium-4 ? Cancer radioimmunotherapy and bone cancer pain relief (Sc-47) Selenium-75 Radiotracer used in brain studies, imaging of adrenal cortex by gamma-scintigraphy, lateral (Se-75) locations of steroid secreting tumors, pancreatic scanning, detection of hyperactive parathyroid glands, measure rate of bile acid loss from the endogenous pool Strontium-85-Bone cancer detection and brain scans (Sr-85), Strontium-89 Bone cancer pain relief, multiple myeloma treatment, and osteoblastic therapy (Sr-89) (Tc-99m) See Molybdenum-99 (Mo-99) (Tc-99m) Thorium-228 Parent of Bismuth-212 (Bi-212) which is an alpha emitter used in cancer radioimmunotherapy (Th-228) Thorium-229 Parent of Actinium-225 (Ac-225) and grandparent of Bismuth-213 (Bi-213) which are alpha (Th-229) emitters used in cancer radioimmunotherapy Thulium-170 Gamma source for blood irradiators, energy source for implanted medical devices (Tm-170) Tin-117m Cancer immunotherapy and bone cancer pain relief (Sn-117m) Parent for Rhenium-188 (Re-188) which is used for cancer diagnostics/treatment, bone cancer pain relief, rheumatoid arthritis treatment, and treatment of blocked arteries (i. e., arteriosclerosis and restenosis) Xenon-127 Neuroimaging of brain disorders, high resolution SPECT studies, pulmonary function tests, and (Xe-127) cerebral blood flow studies Ytterbium-175 Cancer radioimmunotherapy (Yb-175) Yttrium-90 Microseeds obtained from irradiating Yttrium-89 (Y-89) for liver cancer treatment (Y-90) A gamma-emitting label for Yttrium-90 (Y-90) which is used for cancer radioimmunotherapy (i. e., (Y-91) Ymphoma, breast, colon, kidney, lung, ovarian, prostate, pancreatic, and inoperable liver cancers) By"randomized"or grammatical equivalents as herein applied to nucleic acids and proteins is meant that each nucleic acid and peptide consists of essentially random nucleotides and amino acids, respectively. These random peptides (or nucleic acids, discussed herein) can incorporate any nucleotide or amino acid at any position. The synthetic process can be designed to generate randomized proteins or nucleic acids, to allow the formation of all or most of the possible combinations over the length of the sequence, thus forming a library of randomized candidate bioactive proteinaceous agents.

In one embodiment, a library is"fully randomized,"with no sequence preferences or constants at any position. In another embodiment, the library is a"biased random"library. That is, some positions within the sequence either are held constant, or are selected from a limited number of possibilities. For example, the nucleotides or amino acid residues are randomized within a defined class, e. g., of hydrophobic amino acids, hydrophilic residues, sterically biased (either small or large) residues, towards the creation of nucleic acid binding domains, the creation of cysteines, for cross-linking, prolines for SH-3 domains, serines, threonines, tyrosines or histidines for phosphorylation sites, etc., or to purines, etc.

A"recombinant"DNA or RNA molecule is a DNA or RNA molecule that has been subjected to molecular manipulation in vitro.

Non-limiting examples of small molecules include compounds that bind or interact with 109PI D4, ligands including hormones, neuropeptides, chemokines, odorants, phospholipids, and functional equivalents thereof that bind and preferably inhibit 109P1D4 protein function. Such non-limiting small molecules preferably have a molecular weight of less than about 10 kDa, more preferably below about 9, about 8, about 7, about 6, about 5 or about 4 kDa. In certain embodiments, small molecules physically associate with, or bind, 109P1D4 protein ; are not found in naturally occurring metabolic pathways ; and/or are more soluble in aqueous than non-aqueous solutions "Stringency"of hybridization reactions is readily determinable by one of ordinary skill in the art, and generally is an empirical calculation dependent upon probe length, washing temperature, and salt concentration. In general, longer probes require higher temperatures for proper annealing, while shorter probes need lower temperatures. Hybridization generally depends on the ability of denatured nucleic acid sequences to reanneal when complementary strands are present in an environment below their melting temperature. The higher the degree of desired homology between the probe and hybridizable sequence, the higher the relative temperature that can be used. As a result, it follows that higher relative temperatures would tend to make the reaction conditions more stringent, while lower temperatures less so. For additional details and explanation of stringency of hybridization reactions, see Ausubel et al., Current Protocols in Molecular Biology, Wiley Interscience Publishers, (1995).

"Stringent conditions"or"high stringency conditions", as defined herein, are identified by, but not limited to, those that : (1) employ low ionic strength and high temperature for washing, for example 0. 015 M sodium chloride/0. 0015 M sodium citrate/0. 1% sodium dodecyl sulfate at 50oC ; (2) employ during hybridization a denaturing agent, such as formamide, for example, 50% (v/v) formamide with 0. 1% bovine serum albumin/0. 1 % Fico11/0. 1 % polyvinylpyrrolidone/50 mM sodium phosphate buffer at pH 6. 5 with 750 mM sodium chloride, 75 mM sodium citrate at 42 oc ; or (3) employ 50% formamide, 5 x SSC (0. 75 M NaCI, 0. 075 M sodium citrate), 50 mM sodium phosphate (pH 6. 8), 0. 1% sodium pyrophosphate, 5 x Denhardt's solution, sonicated salmon sperm DNA (50 tg/ml), 0. 1 % SDS, and 10% dextran sulfate at 42 oc, with washes at 42OC in 0. 2 x SSC (sodium chloride/sodium. citrate) and 50% formamide at 55 oC, followed by a high-stringency wash consisting of 0. 1 x SSC containing EDTA at 55 oC."Moderately stringent conditions"are described by, but not limited to, those in Sambrook et al., Molecular Cloning : A Laboratory Manual, New York : Cold Spring Harbor Press, 1989, and include the use of washing solution and hybridization conditions (e. g., temperature, ionic strength and % SDS) less stringent than those described above. An example of moderately stringent conditions is overnight incubation at 37OC in a solution comprising : 20% formamide, 5 x SSC (150 mM NaCI, 15 mM trisodium citrate), 50 mM sodium phosphate (pH 7. 6), 5 x Denhardt's solution, 10% dextran sulfate, and 20 mg/mL denatured sheared salmon sperm DNA, followed by washing the filters in 1 x SSC at about 37-500C. The skilled artisan will recognize how to adjust the temperature, ionic strength, etc. as necessary to accommodate factors such as probe length and the like.

An HLA"supermotif'is a peptide binding specificity shared by HLA molecules encoded by two or more HLA alleles.

Overall phenotypic frequencies of HLA-supertypes in different ethnic populations are set forth in Table IV (F). The non- limiting constituents of various supetypes are as follows : A2 : A*0201, A*0202, A*0203, A*0204, A* 0205, A*0206, A*6802, A*6901, A*0207 A3 : A3, A11, A31, A*3301, A*6801, A*0301, A*1101, A*3101 B7 : B7, B*3501-03, B*51, B*5301, B*5401, B*5501, B*5502, B*5601, B*6701, B*7801, B*0702, B*5101, B*5602 B44 : B*3701, B*4402, B*4403, B*60 (B*4001), B61 (B*4006) A1 : A*0102, A*2604, A*3601, A*4301, A*8001 A24 : A*24, A*30, A*2403, A*2404, A*3002, A*3003 B27 : B*1401-02, B*1503, B*1509, B*1510, B*1518, B*3801-02, B*3901, B*3902, B*3903-04, B*4801-02, B*7301, B*2701-08 B58 : B*1516, B*1517, B*5701, B*5702, B58 B62 : B*4601, B52, B*1501 (B62), B*1502 (B75), B*1513 (B77) Calculated population coverage afforded by different HLA-supertype combinations are set forth in Table IV (G).

As used herein"to treat"or"therapeutic"and grammatically related terms, refer to any improvement of any consequence of disease, such as prolonged survival, less morbidity, and/or a lessening of side effects which are the byproducts of an alternative therapeutic modality ; full eradication of disease is not required.

A"transgenic animal" (e. g., a mouse or rat) is an animal having cells that contain a transgene, which transgene was introduced into the animal or an ancestor of the animal at a prenatal, e. g., an embryonic stage. A"transgene"is a DNA that is integrated into the genome of a cell from which a transgenic animal develops.

As used herein, an HLA or cellular immune response"vaccine"is a composition that contains or encodes one or more peptides of the invention. There are numerous embodiments of such vaccines, such as a cocktail of one or more individual peptides ; one or more peptides of the invention comprised by a polyepitopic peptide ; or nucleic acids that encode such individual peptides or polypeptides, e. g., a minigene that encodes a polyepitopic peptide. The"one or more peptides" can include any whole unit integer from 1-150 or more, e. g., at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, or 150 or more peptides of the invention.

The peptides or polypeptides can optionally be modified, such as by lipidation, addition of targeting or other sequences. HLA class I peptides of the invention can be admixed with, or linked to, HLA class 11 peptides, to facilitate activation of both cytotoxic T lymphocytes and helper T lymphocytes. HLA vaccines can also comprise peptide-pulsed antigen presenting cells, e. g., dendritic cells.

The term"variant"refers to a molecule that exhibits a variation from a described type or norm, such as a protein that has one or more different amino acid residues in the corresponding position (s) of a specifically described protein (e. g. the 109P1 D4 protein shown in Figure 2 or Figure 3. An analog is an example of a variant protein. Splice isoforms and single nucleotides polymorphisms (SNPs) are further examples of variants.

The"109P1 D4-related proteins"of the invention include those specifically identified herein, as well as allelic variants, conservative substitution variants, analogs and homologs that can be isolated/generated and characterized without undue experimentation following the methods outlined herein or readily available in the art. Fusion proteins that combine parts of different 109P1 D4 proteins or fragments thereof, as well as fusion proteins of a 109P1 D4 protein and a heterologous polypeptide are also included. Such 109P1D4 proteins are collectively referred to as the 109P1D4-related proteins, the proteins of the invention, or 109P1D4. The term"109P1D4-related protein"refers to a polypeptide fragment or a 109P1D4 protein sequence of 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, or more than 25 amino acids ; or, least30, 35, 40, 45, 50, 55, 60, 65, 70, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190, 195, 200, 225, 250, 275, 300, 325, 350, 375, 400, 425, 450, 475, 500, 525, 550, 575, or 576 or more amino acids.

II.) 109P1D4 Polynucleotides One aspect of the invention provides polynucleotides corresponding or complementary to all or part of a 109P1 D4 gene, mRNA, and/or coding sequence, preferably in isolated form, including polynucleotides encoding a 109P1 D4-related protein and fragments thereof, DNA, RNA, DNA/RNA hybrid, and related molecules, polynucleotides or oligonucleotides complementary to a 109P1 D4 gene or mRNA sequence or a part thereof, and polynucleotides or oligonucleotides that hybridize to a 109P1 D4 gene, mRNA, or to a 109P1 D4 encoding polynucleotide (collectively,"109P1 D4 polynucleotides"). In all instances when referred to in this section, T can also be U in Figure 2.

Embodiments of a 109P1D4 polynucleotide include : a 109P1D4 polynucleotide having the sequence shown in Figure 2, the nucleotide sequence of 109P1 D4 as shown in Figure 2 wherein T is U ; at least 10 contiguous nucleotides of a. polynucleotide having the sequence as shown in Figure 2 ; or, at least 10 contiguous nucleotides of a polynucleotide having the sequence as shown in Figure 2 where T is U. For example, embodiments of 109P1 D4 nucleotides comprise, without limitation : (I) a polynucleotide comprising, consisting essentially of, or consisting of a sequence as shown in Figure 2, wherein T can also be U ; (II) a polynucleotide comprising, consisting essentially of, or consisting of the sequence as shown in Figure 2A, from nucleotide residue number 846 through nucleotide residue number 3911, including the stop codon, wherein T can also be U ; (III) a polynucleotide comprising, consisting essentially of, or consisting of the sequence as shown in Figure 2B, from nucleotide residue number 503 through nucleotide residue number 3667, including the stop codon, wherein T can also be U ; (IV) a polynucleotide comprising, consisting essentially of, or consisting of the sequence as shown in Figure 2C, from nucleotide residue number 846 through nucleotide residue number 4889, including the a stop codon, wherein T can also be U ; (V) a polynucleotide comprising, consisting essentially of, or consisting of the sequence as shown in Figure 2D, from nucleotide residue number 846 through nucleotide residue number 4859, including the stop codon, wherein T can also be U ; (VI) a polynucleotide comprising, consisting essentially of, or consisting of the sequence as shown in Figure 2E, from nucleotide residue number 846 through nucleotide residue number 4778, including the stop codon, wherein T can also be U ; (VI I) a polynucleotide comprising, consisting essentially of, or consisting of the sequence as shown in Figure 2F, from nucleotide residue number 614 through nucleotide residue number 3727, including the stop codon, wherein T can also be U ; (VIII) a polynucleotide comprising, consisting essentially of, or consisting of the sequence as shown in Figure 2G, from nucleotide residue number 735 through nucleotide residue number 3881, including the stop codon, wherein T can also be U ; (IX) a polynucleotide comprising, consisting essentially of, or consisting of the sequence as shown in Figure 2H, from nucleotide residue number 735 through nucleotide residue number 4757, including the stop codon, wherein T can also be U ; (X) a polynucleotide comprising, consisting essentially of, or consisting of the sequence as shown in Figure 21, from nucleotide residue number 514 through nucleotide residue number 3627, including the stop codon, wherein T can also be U ; (XI) a polynucleotide that encodes a 109P1 D4-related protein that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 or 100% homologous to an entire amino acid sequence shown in Figure 2A-I ; (XII) a polynucleotide that encodes a 109P1 D4-related protein that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 or 100% identical to an entire amino acid sequence shown in Figure 2A-I ; (XIII) a polynucleotide that encodes at least one peptide set forth in Tables VIII-XXI and XXII-XLIX ; (XIV) a polynucleotide that encodes a peptide region of at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a peptide of Figures 3A in any whole number increment up to 1021 that includes at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position (s) having a value greater than 0. 5 in the Hydrophilicity profile of Figure 5 ; (XV) a polynucleotide that encodes a peptide region of at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a peptide of Figure 3A in any whole number increment up to 1021 that includes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position (s) having a value less than 0. 5 in the Hydropathicity profile of Figure 6 ; (XVI) a polynucleotide that encodes a peptide region of at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a peptide of Figure 3A in any whole number increment up to 1021 that includes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position (s) having a value greater than 0. 5 in the Percent Accessible Residues profile of Figure 7 ; (XVII) a polynucleotide that encodes a peptide region of at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a peptide of Figure 3A in any whole number increment up to 1021 that includes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position (s) having a value greater than 0. 5 in the Average Flexibility profile of Figure 8 ; (XVIII) a polynucleotide that encodes a peptide region of at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a peptide of Figure 3A in any whole number increment up to 1021 that includes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position (s) having a value greater than 0. 5 in the Beta-turn profile of Figure 9 ; (XIN a polynucleotide that encodes a peptide region of at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a peptide of Figure 3B, 3C, and/or 3D in any whole number increment up to 1054, 1347, and/or 1337 respectively that includes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position (s) having a value greater than 0. 5 in the Hydrophilicity profile of Figure 5 ; (XX) a polynucleotide that encodes a peptide region of at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a peptide of Figure 3B, 3C, and/or 3D in any whole number increment up to 1054, 1347, and/or 1337 respectively that includes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position (s) having a value less than 0. 5 in the Hydropathicity profile of Figure 6 ; (XXI) a polynucleotide that encodes a peptide region of at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a peptide of Figure 3B, 3C, and or 3D in any whole number increment up to 1054, 1347, and/or 1337 respectively that includes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position (s) having a value greater than 0. 5 in the Percent Accessible Residues profile of Figure 7 ; (XXII) a polynucleotide that encodes a peptide region of at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a peptide of Figure 3B, 3C, and/or 3D in any whole number increment up to 1054, 1347, and/or 1337 respectively that includes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position (s) having a value greater than 0. 5 in the Average Flexibility profile of Figure 8 ; (XXV) a polynucleotide that encodes a peptide region of at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a peptide of Figure 3B, 3C, and/or 3D in any whole number increment up to 1054, 1347, and/or 1337 respectively that includes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position (s) having a value greater than 0. 5 in the Beta-turn profile of Figure 9 ; (XXIV) a polynucleotide that encodes a peptide region of at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a peptide of Figure 3E, 3F, 3G, 3H and/or 31 in any whole number increment up to 1310, 1037, 1048, 1340, and/or 1037 respectively that includes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position (s) having a value greater than 0. 5 in the Hydrophilicity profile of Figure 5 ; (XXV) a polynucleotide that encodes a peptide region of at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a peptide of Figure 3E, 3F, 3G, 3H and/or 31 in any whole number increment up to 1310, 1037, 1048, 1340, and/or 1037 respectively that includes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position (s) having a value less than 0. 5 in the Hydropathicity profile of Figure 6 ; (XXVI) a polynucleotide that encodes a peptide region of at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a peptide of Figure 3E, 3F, 3G, 3H and/or 31 in any whole number increment up to 1310, 1037, 1048, 1340, and/or 1037 respectively that includes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position (s) having a value greater than 0. 5 in the Percent Accessible Residues profile of Figure 7 ; (XXVII) a polynucleotide that encodes a peptide region of at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a peptide of Figure 3E, 3F, 3G, 3H and/or 31 in any whole number increment up to 1310, 1037, 1048, 1340, and/or 1037 respectively that includes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position (s) having a value greater than 0. 5 in the Average Flexibility profile of Figure 8 ; (XXVIII) a polynucleotide that encodes a peptide region of at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a peptide of Figure 3E, 3F, 3G, 3H, and/or 31 in any whole number increment up to 1310, 1037, 1048, 1340, and/or 1037 respectively that includes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position (s) having a value greater than 0. 5 in the Beta-turn profile of Figure 9 ; (XXIX) a polynucleotide that is fully complementary to a polynucleotide of any one of (I)- (XXVIII) ; (XXX) a polynucleotide that is fully complementary to a polynucleotide of any one of (I)- (XXIX) ; (XXXI) a peptide that is encoded by any of (I) to (XXX) ; and ; (XXXII) a composition comprising a polynucleotide of any of (I)- (XXX) or peptide of (XXXI) together with a pharmaceutical excipient and/or in a human unit dose form ; (XXXIII) a method of using a polynucleotide of any (I)- (XXX) or peptide of (XXXI) or a composition of (XXXII) in a method to modulate a cell expressing 109P1 D4 ; (XXXIV) a method of using a polynucleotide of any (I)- (XXX) or peptide of (XXXI) or a composition of (XXXII) in a method to diagnose, prophylax, prognose, or treat an individual who bears a cell expressing 109P1D4 ; (XXXV) a method of using a polynucleotide of any (I)- (XXX) or peptide of (XXXI) or a composition of (XXXII) in a method to diagnose, prophylax, prognose, or treat an individual who bears a cell expressing 109P1D4, said cell from a cancer of a tissue listed in Table I ; (XXXVI) a method of using a polynucleotide of any (I)- (XXX) or peptide of (XXXI) or a composition of (XXXII) in a method to diagnose, prophylax, prognose, or treat a a cancer ; (XXXVII) a method of using a polynucleotide of any (I)- (XXX) or peptide of (XXXI) or a composition of (XXXII) in a method to diagnose, prophylax, prognose, or treat a a cancer of a tissue listed in Table 1 ; and ; (XXXVIII) a method of using a polynucleotide of any (I)- (XXX) or peptide of (XXXI) or a composition of (XXXII) in a method to identify or characterize a modulator of a cell expressing 109P1 D4.

As used herein, a range is understood to disclose specifically all whole unit positions thereof.

Typical embodiments of the invention disclosed herein include 109P1 D4 polynucleotides that encode specific portions of 109P1D4 mRNA sequences (and those which are complementary to such sequences) such as those that encode the proteins and/or fragments thereof, for example :.

(a) 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190, 195, 200, 225, 250, 275, 300, 325, 350, 375, 400, 425, 450, 475, 500, 525, 550, 575, 600, 625, 650, 675, 700, 725, 750, 775, 800, 825, 850, 875, 900, 925, 950, 975, 1000, 1010, 1020, and 1021 or more contiguous amino acids of 109P1 D4 variant 1 ; the maximal lengths relevant for other variants are : variant 2, 1054 amino acids ; variant 3, 1347 amino acids, variant 4, 1337 amino acids, variant 5, 1310 amino acids, variant 6 ; 1047 amino acids, variant 7 ; 1048 amino acids, variant 8 ; 1340 amino acids and variant 9 ; 1037 amoni acids.

For example, representative embodiments of the invention disclosed herein include : polynucleotides and their encoded peptides themselves encoding about amino acid 1 to about amino acid 10 of the 109P1 D4 protein shown in Figure 2 or Figure 3, polynucleotides encoding about amino acid 10 to about amino acid 20 of the 109P1 D4 protein shown in Figure 2 or Figure 3, polynucleotides encoding about amino acid 20 to about amino acid 30 of the 109P1 D4 protein shown in Figure 2 or Figure 3, polynucleotides encoding about amino acid 30 to about amino acid 40 of the 109P1 D4 protein shown in Figure 2 or Figure 3, polynucleotides encoding about amino acid 40 to about amino acid 50 of the 109P1 D4 protein shown in Figure 2 or Figure 3, polynucleotides encoding about amino acid 50 to about amino acid 60 of the 109P1 D4 protein shown in Figure 2 or Figure 3, polynucleotides encoding about amino acid 60 to about amino acid 70 of the 109P1 D4 protein shown in Figure 2 or Figure 3, polynucleotides encoding about amino acid 70 to about amino acid 80 of the 109P1 D4 protein shown in Figure 2 or Figure 3, polynucleotides encoding about amino acid 80 to about amino acid 90 of the 109P1 D4 protein shown in Figure 2 or Figure 3, polynucleotides encoding about amino acid 90 to about amino acid 100 of the 109P1 D4 protein shown in Figure 2 or Figure 3, in increments of about 10 amino acids, ending at the carboxyl terminal amino acid set forth in Figure 2 or Figure 3. Accordingly, polynucleotides encoding portions of the amino acid sequence (of about 10 amino acids), of amino acids, 100 through the carboxyl terminal amino acid of the 109P1 D4 protein are embodiments of the invention. Wherein it is understood that each particular amino acid position discloses that position plus or minus five amino acid residues.

Polynucleotides encoding relatively long portions of a 109P1 D4 protein are also within the scope of the invention.

For example, polynucleotides encoding from about amino acid 1 (or 20 or 30 or 40 etc.) to about amino acid 20, (or 30, or 40 or 50 etc.) of the 109P1 D4 protein"or variant"shown in Figure 2 or Figure 3 can be generated by a variety of techniques well known in the art. These polynucleotide fragments can include any portion of the 109P1 D4 sequence as shown in Figure 2.

Additional illustrative embodiments of the invention disclosed herein include 109P1 D4 polynucleotide fragments encoding one or more of the biological motifs contained within a 109P1 D4 protein"or variant"sequence, including one or more of the motif-bearing subsequences of a 109P1 D4 protein"or variant"set forth in Tables VIII-XXI and XXII-XLIX. In another embodiment, typical polynucleotide fragments of the invention encode one or more of the regions of 109P1 D4 protein or variant that exhibit homology to a known molecule. In another embodiment of the invention, typical polynucleotide fragments can encode one or more of the 109P1 D4 protein or variant N-glycosylation sites, cAMP and cGMP-dependent protein kinase phosphorylation sites, casein kinase 11 phosphorylation sites or N-myristoylation site and amidation sites.

Note that to determine the starting position of any peptide set forth in Tables VIII-XXI and Tables XXII to XLIX (collectively HLA Peptide Tables) respective to its parental protein, e. g., variant 1, variant 2, etc., reference is made to three factors : the particular variant, the length of the peptide in an HLA Peptide Table, and the Search Peptides listed in Table VII.

Generally, a unique Search Peptide is used to obtain HLA peptides for a particular variant. The position of each Search Peptide relative to its respective parent molecule is listed in Table VII. Accordingly, if a Search Peptide begins at position "X", one must add the value"X minus 1"to each position in Tables VIII-XXI and Tables XXII-IL to obtain the actual position of the HLA peptides in their parental molecule. For example if a particular Search Peptide begins at position 150 of its parental molecule, one must add 150-1, i. e., 149 to each HLA peptide amino acid position to calculate the position of that amino acid in the parent molecule.

Il. A.) Uses of 109P1D4 Polynucleotides II. A. 1.) Monitoring of Genetic Abnormalities The polynucleotides of the preceding paragraphs have a number of different specific uses. The human 109P1 D4 gene maps to the chromosomal location set forth in the Example entitled"Chromosomal Mapping of 109P1 D4."For example, because the 109P1 D4 gene maps to this chromosome, polynucleotides that encode different regions of the 109P1D4 proteins are used to characterize cytogenetic abnormalities of this chromosomal locale, such as abnormalities that are identified as being associated with various cancers. In certain genes, a variety of chromosomal abnormalities including rearrangements have been identified as frequent cytogenetic abnormalities in a number of different cancers (see e. g.

Krajinovic et al., Mutat. Res. 382 (3-4) : 81-83 (1998) ; Johansson et al., Blood 86 (10) : 3905-3914 (1995) and Finger et al., P. N. A. S. 85 (23) : 9158-9162 (1988)). Thus, polynucleotides encoding specific regions of the 109P1D4 proteins provide new tools that can be used to delineate, with greater precision than previously possible, cytogenetic abnormalities in the chromosomal region that encodes 109P1 D4 that may contribute to the malignant phenotype. In this context, these polynucleotides satisfy a need in the art for expanding the sensitivity of chromosomal screening in order to identify more subtle and less common chromosomal abnormalities (see e. g. Evans et al., Am. J. Obstet. Gynecol 171 (4) : 1055-1057 (1994)).

Furthermore, as 109P1 D4 was shown to be highly expressed in prostate and other cancers, 109P1 D4 polynucleotides are used in methods assessing the status of 109P1D4 gene products in normal versus cancerous tissues.

Typically, polynucleotides that encode specific regions of the 109P1 D4 proteins are used to assess the presence of perturbations (such as deletions, insertions, point mutations, or alterations resulting in a loss of an antigen etc.) in specific regions of the 109P1 D4 gene, such as regions containing one or more motifs. Exemplary assays include both RT-PCR assays as well as single-strand conformation polymorphism (SSCP) analysis (see, e. g., Marrogi et al., J. Cutan. Pathol.

26 (8) : 369-378 (1999), both of which utilize polynucleotides encoding specific regions of a protein to examine these regions within the protein.

Il. A. 2.) Antisense Embodiments Other specifically contemplated nucleic acid related embodiments of the invention disclosed herein are genomic DNA, cDNAs, ribozymes, and antisense molecules, as well as nucleic acid molecules based on an alternative backbone, or including alternative bases, whether derived from natural sources or synthesized, and include molecules capable of inhibiting the RNA or protein expression of 109P1 D4. For example, antisense molecules can be RNAs or other molecules, including peptide nucleic acids (PNAs) or non-nucleic acid molecules such as phosphorothioate derivatives that specifically bind DNA or RNA in a base pair-dependent manner. A skilled artisan can readily obtain these classes of nucleic acid molecules using the 109P1 D4 polynucleotides and polynucleotide sequences disclosed herein.

Antisense technology entails the administration of exogenous oligonucleotides that bind to a target polynucleotide located within the cells. The term"antisense"refers to the fact that such oligonucleotides are complementary to their intracellular targets, e. g., 109P1 D4. See for example, Jack Cohen, Oligodeoxynucleotides, Antisense Inhibitors of Gene Expression, CRC Press, 1989 ; and Synthesis 1 : 1-5 (1988). The 109P1 D4 antisense oligonucleotides of the present invention include derivatives such as S-oligonucleotides (phosphorothioate derivatives or S-oligos, see, Jack Cohen, supra), which exhibit enhanced cancer cell growth inhibitory action. S-oligo (nucleoside phosphorothioates) are isoelectronic analogs of an oligonucleotide (0-oligo) in which a nonbridging oxygen atom of the phosphate group is replaced by a sulfur atom. The S-oligo of the present invention can be prepared by treatment of the corresponding 0-oligo with 3H-1, 2- benzodithiol-3-one-1, 1-dioxide, which is a sulfur transfer reagent. See, e. g., lyer, R. P. et al., J. Org. Chem. 55 : 4693-4698 (1990) ; and lyer, R. P. et al., J. Am. Chem. Soc. 112 : 1253-1254 (1990). Additional 109Pl D4 antsense oligonucleotides of the present invention include morpholino antisense oligonucleotides known in the art (see, e. g., Partridge et al., 1996, Antisense & Nucleic Acid Drug Development 6 : 169-175).

The 109P1 D4 antisense oligonucleotides of the present invention typically can be RNA or DNA that is complementary to and stably hybridizes with the first 100 5'codons or last 100 3'codons of a 109P1 D4 genomic sequence or the corresponding mRNA. Absolute complementarity is not required, although high degrees of complementarity are preferred. Use of an oligonucleotide complementary to this region allows for the selective hybridization to 109P1 D4 mRNA and not to mRNA specifying other regulatory subunits of protein kinase. In one embodiment, 109P1 D4 antisense oligonucleotides of the present invention are 15 to 30-mer fragments of the antisense DNA molecule that have a sequence that hybridizes to 109P1 D4 mRNA. Optionally, 109P1 D4 antisense oligonucleotide is a 30-mer oligonucleotide that is complementary to a region in the first 10 5'codons or last 10 3'codons of 109P1 D4. Alternatively, the antisense molecules are modified to employ ribozymes in the inhibition of 109P1 D4 expression, see, e. g., L. A. Couture & D. T. Stinchcomb ; Trends Genet 12 : 510-515 (1996).

Il. A. 3.) Primers and Primer Pairs Further specific embodiments of these nucleotides of the invention include primers and primer pairs, which allow the specific amplification of polynucleotdes of the invention or of any specific parts thereof, and probes that selectively or specifically hybridize to nucleic acid molecules of the invention or to any part thereof. Probes can be labeled with a detectable marker, such as, for example, a radioisotope, fluorescent compound, bioluminescent compound, a chemiluminescent compound, metal chelator or enzyme. Such probes and primers are used to detect the presence of a 109P1 D4 polynucleotide in a sample and as a means for detecting a cell expressing a 109P1 D4 protein.

Examples of such probes include polypeptides comprising all or part of the human 109P1 D4 cDNA sequence shown in Figure 2. Examples of primer pairs capable of specifically amplifying 109P1 D4 mRNAs are also described in the Examples. As will be understood by the skilled artisan, a great many different primers and probes can be prepared based on the sequences provided herein and used effectively to amplify and/or detect a 109P1 D4 mRNA.

The 109P1 D4 polynucleotides of the invention are useful for a variety of purposes, including but not limited to their use as probes and primers for the amplification and/or detection of the 109P1 D4 gene (s), mRNA (s), or fragments thereof ; as reagents for the diagnosis and/or prognosis of prostate cancer and other cancers ; as coding sequences capable of directing the expression of 109P1 D4 polypeptides ; as tools for modulating or inhibiting the expression of the 109P1 D4 gene (s) and/or translation of the 109P1 D4 transcript (s) ; and as therapeutic agents.

The present invention includes the use of any probe as described herein to identify and isolate a 109P1 D4 or 109P1 D4 related nucleic acid sequence from a naturally occurring source, such as humans or other mammals, as well as the isolated nucleic acid sequence perse, which would comprise all or most of the sequences found in the probe used.

Il. A. 4.) Isolation of 109P1 D4-Encoding Nucleic Acid Molecules The 109P1 D4 cDNA sequences described herein enable the isolation of other polynucleotides encoding 109P1 D4 gene product (s), as well as the isolation of polynucleotides encoding 109P1 D4 gene product homologs, alternatively spliced isoforms, allelic variants, and mutant forms of a 109P1 D4 gene product as well as polynucleotides that encode analogs of 109P1 D4-related proteins. Various molecular cloning methods that can be employed to isolate full length cDNAs encoding a 109P1 D4 gene are well known (see, for example, Sambrook, J. et aL, Molecular Cloning : A Laboratory Manual, 2d edition, Cold Spring Harbor Press, New York, 1989 ; Current Protocols in Molecular Biology. Ausubel et al., Eds., Wiley and Sons, 1995). For example, lambda phage cloning methodologies can be conveniently employed, using commercially available cloning systems (e. g., Lambda ZAP Express, Stratagene). Phage clones containing 109P1D4 gene cDNAs can be identified by probing with a labeled 109P1D4 cDNA or a fragment thereof. For example, in one embodiment, a 109P1 D4 cDNA (e. g., Figure 2) or a portion thereof can be synthesized and used as a probe to retrieve overlapping and full-length cDNAs corresponding to a 109P1 D4 gene. A 109P1 D4 gene itself can be isolated by screening genomic DNA libraries, bacterial artificial chromosome libraries (BACs), yeast artificial chromosome libraries (YACs), and the like, with 109P1D4 DNA probes or primers.

Il. A. 5.) Recombinant Nucleic Acid Molecules and Host-Vector Systems The invention also provides recombinant DNA or RNA molecules containing a 109P1 D4 polynucleotide, a fragment, analog or homologue thereof, including but not limited to phages, plasmids, phagemids, cosmids, YACs, BACs, as well as various viral and non-viral vectors well known in the art, and cells transformed or transfected with such recombinant DNA or RNA molecules. Methods for generating such molecules are well known (see, for example, Sambrook et al., 1989, supra).

The invention further provides a host-vector system comprising a recombinant DNA molecule containing a 109P1 D4 polynucleotide, fragment, analog or homologue thereof within a suitable prokaryotic or eukaryotic host cell. Examples of suitable eukaryotic host cells include a yeast cell, a plant cell, or an animal cell, such as a mammalian cell or an insect cell (e. g., a baculovirus-infectible cell such as an Sf9 or HighFive cell). Examples of suitable mammalian cells include various prostate cancer cell lines such as DU145 and TsuPrl, other transfectable or transducible prostate cancer cell lines, primary cells (PrEC), as well as a number of mammalian cells routinely used for the expression of recombinant proteins (e. g., COS, CHO, 293, 293T cells). More particularly, a polynucleotide comprising the coding sequence of 109P1 D4 or a fragment, analog or homolog thereof can be used to generate 109P1 D4 proteins or fragments thereof using any number of host-vector systems routinely used and widely known in the art.

A wide range of host-vector systems suitable for the expression of 109P1 D4 proteins or fragments thereof are available, see for example, Sambrook et al., 1989, supra ; Current Protocols in Molecular Biology, 1995, supra). Preferred vectors for mammalian expression include but are not limited to pcDNA 3. 1 myc-His-tag (Invitrogen) and the retroviral vector pSRatkneo (Muller et al., 1991, MCB 11 : 1785). Using these expression vectors, 109P1 D4 can be expressed in several prostate cancer and non-prostate cell lines, including for example 293, 293T, rat-1, NIH 3T3 and TsuPrl. The host-vector systems of the invention are useful for the production of a 109P1 D4 protein or fragment thereof. Such host-vector systems can be employed to study the functional properties of 109P1 D4 and 109P1 D4 mutations or analogs.

Recombinant human 109P1 D4 protein or an analog or homolog or fragment thereof can be produced by mammalian cells transfected with a construct encoding a 109P1 D4-related nucleotide. For example, 293T cells can be transfected with an expression plasmid encoding 109P1 D4 or fragment, analog or homolog thereof, a 109P1 D4-related protein is expressed in the 293T cells, and the recombinant 109P1 D4 protein is isolated using standard purification methods (e. g., affinity purification using anti-109P1 D4 antibodies). In another embodiment, a 109P1 D4 coding sequence is subcloned into the retroviral vector pSRaMSVtkneo and used to infect various mammalian cell lines, such as NIH 3T3, TsuPrl, 293 and rat-1 in order to establish 109P1 D4 expressing cell lines. Various other expression systems well known in the art can also be employed. Expression constructs encoding a leader peptide joined in frame to a 109P1 D4 coding sequence can be used for the generation of a secreted form of recombinant 109P1 D4 protein.

As discussed herein, redundancy in the genetic code permits variation in 109P1 D4 gene sequences. In particular, it is known in the art that specific host species often have specific codon preferences, and thus one can adapt the disclosed sequence as preferred for a desired host. For example, preferred analog codon sequences typically have rare codons (i. e., codons having a usage frequency of less than about 20% in known sequences of the desired host) replaced with higher frequency codons. Codon preferences for a specific species are calculated, for example, by utilizing codon usage tables available on the INTERNET such as at URL dna. affrc. go. jp/-nakamura/codon. html.

Additional sequence modifications are known to enhance protein expression in a cellular host. These include elimination of sequences encoding spurious polyadenylation signals, exon/intron splice site signals, transposon-like repeats, and/or other such well-characterized sequences that are deleterious to gene expression. The GC content of the sequence is adjusted to levels average for a given cellular host, as calculated by reference to known genes expressed in the host cell.

Where possible, the sequence is modified to avoid predicted hairpin secondary mRNA structures. Other useful modifications include the addition of a translational initiation consensus sequence at the start of the open reading frame, as described in Kozak, Mol. Cell Biol., 9 : 5073-5080 (1989). Skilled artisans understand that the general rule that eukaryotic ribosomes initiate translation exclusively at the 5'proximal AUG codon is abrogated only under rare conditions (see, e. g., Kozak PNAS 92 (7) : 2662-2666, (1995) and Kozak NAR 15 (20) : 8125-8148 (1987)).

III.) 109P1 D4-related Proteins Another aspect of the present invention provides 109P1 D4-related proteins. Specific embodiments of 109P1 D4 proteins comprise a polypeptide having all or part of the amino acid sequence of human 109P1 D4 as shown in Figure 2 or Figure 3. Alternatively, embodiments of 109P1 D4 proteins comprise variant, homolog or analog polypeptides that have alterations in the amino acid sequence of 109P1 D4 shown in Figure 2 or Figure 3.

Embodiments of a 109P1 D4 polypeptide include : a 109P1 D4 polypeptide having a sequence shown in Figure 2, a peptide sequence of a 109P1 D4 as shown in Figure 2 wherein T is U ; at least 10 contiguous nucleotides of a polypeptide having the sequence as shown in Figure 2 ; or, at least 10 contiguous peptides of a polypeptide having the sequence as shown in Figure 2 where T is U. For example, embodiments of 109P1 D4 peptides comprise, without limitation : (I) a protein comprising, consisting essentially of, or consisting of an amino acid sequence as shown in Figure 2A-I or Figure 3A-I ; (II) a 109P1 D4-related protein that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 or 100% homologous to an entire amino acid sequence shown in Figure 2A-I or 3A-I ; (III) a 109P1 D4-related protein that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 or 100% identical to an entire amino acid sequence shown in Figure 2A-I or 3A-I ; (IV) a protein that comprises at least one peptide set forth in Tables VIII to XLIX, optionally with a proviso that it is not an entire protein of Figure 2 ; (V) a protein that comprises at least one peptide set forth in Tables VIII-XXI, collectively, which peptide is also set forth in Tables XXII to XLIX, collectively, optionally with a proviso that it is not an entire protein of Figure 2 ; (VI) a protein that comprises at least two peptides selected from the peptides set forth in Tables VIII-XLIX, optionally with a proviso that it is not an entire protein of Figure 2 ; (VII) a protein that comprises at least two peptides selected from the peptides set forth in Tables Viii to XLIX collectively, with a proviso that the protein is not a contiguous sequence from an amino acid sequence of Figure 2 ; (VIII) a protein that comprises at least one peptide selected from the peptides set forth in Tables VIII-XXI ; and at least one peptide selected from the peptides set forth in Tables XXII to XLIX, with a proviso that the protein is not a contiguous sequence from an amino acid sequence of Figure 2 ; (IX) a polypeptide comprising at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a protein of Figure 3A, 3B, 3C, 3D and/or 3E in any whole number increment up to 1021, 1054, 1347, 1337, and/or 1310 respectively that includes at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position (s) having a value greater than 0. 5 in the Hydrophilicity profile of Figure 5 ; (X) a polypeptide comprising at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a protein of Figure 3A, 3B, 3C, 3D, and/or 3E, in any whole number increment up to 1021, 1054, 1347, 1337, and/or 1310 respectively respectively that includes at least at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position (s) having a value less than 0. 5 in the Hydropathicity profile of Figure 6 ; (Xl) apolypeptidecomprisingatleast5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a protein of Figure 3A, 3B, 3C, 3D, and/or 3E, in any whole number increment up to 1021, 1054, 1347, 1337, and/or 1310 respectively respectively that includes at least at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position (s) having a value greater than 0. 5 in the Percent Accessible Residues profile of Figure 7 ; (XI 1) a polypeptide comprising at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a protein of Figure 3A, 3B, 3C, 3D, and/or 3E, in any whole number increment up to 1021, 1054, 1347, 1337, and/or 1310 respectively respectively that includes at least at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position (s) having a value greater than 0. 5 in the Average Flexibility profile of Figure 8 ; (XIII) a polypeptide comprising at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, amino acids of a protein of Figure 3A, 3B, 3C, 3D, and 3E in any whole number increment up to 1021, 1054, 1347, 1337, and/or 1310 respectively respectively that includes at least at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position (s) having a value greater than 0. 5 in the Beta-turn profile of Figure 9 ; (XIV) a polypeptide comprising at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a protein of Figure 3F, 3G, 3H, and/or 31, in any whole number increment up to 1037, 1048, 1340, and/or 1037 respectively that includes at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position (s) having a value greater than 0. 5 in the Hydrophilicity profile of Figure 5 ; (XV) a polypeptide comprising at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a protein of Figure 3F, 3G, 3H, and/or 31 in any whole number increment up to 1037, 1048, 1340, and/or 1037 respectively that includes at least at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position (s) having a value less than 0. 5 in the Hydropathicity profile of Figure 6 ; (XVI) a polypeptide comprising at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a protein of Figure 3F, 3G, 3H, and/or 31 in any whole number increment up to 1037, 1048, 1340, and/or 1037 respectively that includes at least at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position (s) having a value greater than 0. 5 in the Percent Accessible Residues profile of Figure 7 ; (XVII) a polypeptide comprising at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a protein of Figure 3F, 3G, 3H, and/or 31 in any whole number increment up to 1037, 1048, 1340, and/or 1037 respectively that includes at least at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position (s) having a value greater than 0. 5 in the Average Flexibility profile of Figure 8 ; (XVIII) a polypeptide comprising at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, amino acids of a protein of Figure 3F, 3G, 3H, and/or 31 in any whole number increment up to 1037, 1048, 1340, and/or 1037 respectively that includes at least at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position (s) having a value greater than 0. 5 in the Beta-turn profile of Figure 9 ; (XIX) a peptide that occurs at least twice in Tables VIII-XXI and XXII to XLIX, collectively ; (XX) a peptide that occurs at least three times in Tables VIII-XX and XXII to XLIX, collectively ; (XXI) a peptide that occurs at least four times in Tables VIII-XXI and XXII to XLIX, collectively ; (XXII) a peptide that occurs at least five times in Tables VIII-XXI and XXlI to XLIX, collectively ; (XXIII) a peptide that occurs at least once in Tables VIII-XXI, and at least once in tables XXII to XLIX ; (XXIV) a peptide that occurs at least once in Tables VIII-XXI, and at least twice in tables XXII to XLIX ; (XXV) a peptide that occurs at least twice in Tables VIII-XXI, and at least once in tables XXII to XLIX ; (XXVI) a peptide that occurs at least twice in Tables Vill-XXI, and at least twice in tables XXII to XLIX ; (XXVII) a peptide which comprises one two, three, four, or five of the following characteristics, or an oligonucleotide encoding such peptide : i) a region of at least 5 amino acids of a particular peptide of Figure 3, in any whole number increment up to the full length of that protein in Figure 3, that includes an amino acid position having a value equal to or greater than 0. 5, 0. 6, 0. 7, 0. 8, 0. 9, or having a value equal to 1. 0, in the Hydrophilicity profile of Figure 5 ; ii) a region of at least 5 amino acids of a particular peptide of Figure 3, in any whole number increment up to the full length of that protein in Figure 3, that includes an amino acid position having a value equal to or less than 0. 5, 0. 4, 0. 3, 0. 2, 0. 1, or having a value equal to 0. 0, in the Hydropathicity profile of Figure 6 ; iii) a region of at least 5 amino acids of a particular peptide of Figure 3, in any whole number increment up to the full length of that protein in Figure 3, that includes an amino acid position having a value equal to or greater than 0. 5, 0. 6, 0. 7, 0. 8, 0. 9, or having a value equal to 1. 0, in the Percent Accessible Residues profile of Figure 7 ; iv) a region of at least 5 amino acids of a particular peptide of Figure 3, in any whole number increment up to the full length of that protein in Figure 3, that includes an amino acid position having a value equal to or greater than 0. 5, 0. 6, 0. 7, 0. 8, 0. 9, or having a value equal to 1. 0, in the Average Flexibility profile of Figure 8 ; or, v) a region of at least 5 amino acids of a particular peptide of Figure 3, in any whole number increment up to the full length of that protein in Figure 3, that includes an amino acid position having a value equal to or greater than 0. 5, 0. 6, 0. 7, 0. 8, 0. 9, or having a value equal to 1. 0, in the Beta-turn profile of Figure 9 ; ; (XXVIII) a composition comprising a peptide of (I)- (XXVII) or an antibody or binding region thereof together with a pharmaceutical excipient and/or in a human unit dose form.

(XXIX) a method of using a peptide of (I)- (XXVIi), or an antibody or binding region thereof or a composition of (XXVIII) in a method to modulate a cell expressing 109P1D4, ; (XXX) a method of using a peptide of (I)- (XXVII) or an antibody or binding region thereof or a composition of (XXVIII) in a method to diagnose, prophylax, prognose, or treat an individual who bears a cell expressing 109P1 D4 ; (XXXI) a method of using a peptide of (I)- (XXVII) or an antibody or binding region thereof or a composition (XXVIII) in a method to diagnose, prophylax, prognose, or treat an individual who bears a cell expressing 109P1D4, said cell from a cancer of a tissue listed in Table I ; (XXXII) a method of using a peptide of (I)-(XXVII) or an antibody or binding region thereof or a composition of (XXVIII) in a method to diagnose, prophylax, prognose, or treat a a cancer, (XXXIII) a method of using a peptide of (I)- (XXVII) or an antibody or binding region thereof or a composition of (XXVIII) in a method to diagnose, prophylax, prognose, or treat a a cancer of a tissue listed in Table I ; and ; (XXXIV) a method of using a a peptide of (I)- (XXVII) or an antibody or binding region thereof or a composition (XXVIII) in a method to identify or characterize a modulator of a cell expressing 109P1 D4 As used herein, a range is understood to specifically disclose all whole unit positions thereof.

Typical embodiments of the invention disclosed herein include 109P1 D4 polynucleotides that encode specific portions of 109P1D4 mRNA sequences (and those which are complementary to such sequences) such as those that encode the proteins and/or fragments thereof, for example : (a) 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190, 195, 200, 225, 250, 275, 300, 325, 350, 375, 400, 425, 450, 475, 500, 525, 550, 575, 600, 625, 650, 675, 700, 725, 750, 775, 800, 825, 850, 875, 900, 925, 950, 975, 1000, 1010, 1020, and 1021 or more contiguous amino acids of 109P1 D4 variant 1 ; the maximal lengths relevant for other variants are : variant 2, 1054 amino acids ; variant 3, 1347 amino acids, variant 4, 1337 amino acids, variant 5, 1310 amino acids, variant 6 ; 1037 amino acids, variant 7 ; 1048 amino acids, variant 8 ; 1340 amino acids, and variant 9 ; 1037 amino acids..

In general, naturally occurring allelic variants of human 109P1 D4 share a high degree of structural identity and homology (e. g., 90% or more homology). Typically, allelic variants of a 109P1 D4 protein contain conservative amino acid substitutions within the 109P1 D4 sequences described herein or contain a substitution of an amino acid from a corresponding position in a homologue of 109P1 D4. One class of 109P1 D4 allelic variants are proteins that share a high degree of homology with at least a small region of a particular 109P1 D4 amino acid sequence, but further contain a radical departure from the sequence, such as a non-conservative substitution, truncation, insertion or frame shift. In comparisons of protein sequences, the terms, similarity, identity, and homology each have a distinct meaning as appreciated in the field of genetics. Moreover, orthology and paralogy can be important concepts describing the relationship of members of a given protein family in one organism to the members of the same family in other organisms.

Amino acid abbreviations are provided in Table II. Conservative amino acid substitutions can frequently be made in a protein without altering either the conformation or the function of the protein. Proteins of the invention can comprise 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 conservative substitutions. Such changes include substituting any of isoleucine (I), valine (V), and leucine (L) for any other of these hydrophobic amino acids ; aspartic acid (D) for glutamic acid (E) and vice versa ; glutamin (Q) for asparagine (N) and vice versa ; and serine (S) for threonine (T) and vice versa. Other substitutions can also be considered conservative, depending on the environment of the particular amino acid and its role in the three- dimensional structure of the protein. For example, glycine (G) and alanine (A) can frequently be interchangeable, as can alanine (A) and valine (V). Methionine (M), which is relatively hydrophobic, can frequently be interchanged with leucine and isoleucine, and sometimes with valine. Lysine (K) and arginine (R) are frequently interchangeable in locations in which the significant feature of the amino acid residue is its charge and the differing pK's of these two amino acid residues are not significant. Still other changes can be considered"conservative"in particular environments (see, e. g. Table III herein ; pages 13-15"Biochemistry"2nd ED, Lubert Stryer ed (Stanford University) ; Henikoff et al., PNAS 1992 Vol 89 10915-10919 ; Lei et a/., J Biol Chem 1995 May 19 ; 270 (20) : 11882-6).

Embodiments of the invention disclosed herein include a wide variety of art-accepted variants or analogs of 109P1D4 proteins such as polypeptides having amino acid insertions, deletions and substitutions. 109P1D4 variants can be made using methods known in the art such as site-directed mutagenesis, alanine scanning, and PCR mutagenesis. Site- directed mutagenesis (Carter et al., Nucl. Acids Re&, 13 : 4331 (1986) ; Zoller et al., Nucl. Acids Res., 10 : 6487 (1987)), cassette mutagenesis (Wells et a/., Gene, 34 : 315 (1985)), restriction selection mutagenesis (Wells et al., Philos. Trans. R.

Soc. London SerA, 317 : 415 (1986)) or other known techniques can be performed on the cloned DNA to produce the 109P1 D4 variant DNA.

Scanning amino acid analysis can also be employed to identify one or more amino acids along a contiguous sequence that is involved in a specific biological activity such as a protein-protein interaction. Among the preferred scanning amino acids are relatively small, neutral amino acids. Such amino acids include alanine, glycine, serine, and cysteine.

Alanine is typically a preferred scanning amino acid among this group because it eliminates the side-chain beyond the beta- carbon and is less likely to alter the main-chain conformation of the variant. Alanine is also typically preferred because it is the most common amino acid. Further, it is frequently found in both buried and exposed positions (Creighton, The Proteins, (W. H. Freeman & Co., N. Y.) ; Chothia, J. Mol. Biol., 150 : 1 (1976)). If alanine substitution does not yield adequate amounts of variant, an isosteric amino acid can be used.

As defined herein, 109P1 D4 variants, analogs or homologs, have the distinguishing attribute of having at least one epitope that is"cross reactive"with a 109P1 D4 protein having an amino acid sequence of Figure 3. As used in this sentence,"cross reactive » means that an antibody or T cell that specifically binds to a 109P1 D4 variant also specifically binds to a 109P1 D4 protein having an amino acid sequence set forth in Figure 3. A polypeptide ceases to be a variant of a protein shown in Figure 3, when it no longer contains any epitope capable of being recognized by an antibody or T cell that specifically binds to the starting 109P1D4 protein. Those skilled in the art understand that antibodies that recognize proteins bind to epitopes of varying size, and a grouping of the order of about four or five amino acids, contiguous or not, is regarded as a typical number of amino acids in a minimal epitope. See, e. g., Nair et al., J. Immunol 2000 165 (12) : 6949-6955 ; Hebbes et al., Mol lmmunol (1989) 26 (9) : 865-73 ; Schwartz et al., J Immunol (1985) 135 (4) : 2598-608.

Other classes of 109P1 D4-related protein variants share 70%, 75%, 80%, 85% or 90% or more similarity with an amino acid sequence of Figure 3, or a fragment thereof. Another specific class of 109P1 D4 protein variants or analogs comprises one or more of the 109P1 D4 biological motifs described herein or presently known in the art. Thus, encompassed by the present invention are analogs of 109P1 D4 fragments (nucleic or amino acid) that have altered functional (e. g. immunogenic) properties relative to the starting fragment. It is to be appreciated that motifs now or which become part of the art are to be applied to the nucleic or amino acid sequences of Figure 2 or Figure 3.

As discussed herein, embodiments of the claimed invention include polypeptides containing less than the full amino acid sequence of a 109P1 D4 protein shown in Figure 2 or Figure 3. For example, representative embodiments of the invention comprise peptides/proteins having any 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more contiguous amino acids of a 109P1 D4 protein shown in Figure 2 or Figure 3.

Moreover, representative embodiments of the invention disclosed herein include polypeptides consisting of about amino acid 1 to about amino acid 10 of a 109P1 D4 protein shown in Figure 2 or Figure 3, polypeptides consisting of about amino acid 10 to about amino acid 20 of a 109P1 D4 protein shown in Figure 2 or Figure 3, polypeptides consisting of about amino acid 20 to about amino acid 30 of a 109P1D4 protein shown in Figure 2 or Figure 3, polypeptides consisting of about amino acid 30 to about amino acid 40 of a 109P1 D4 protein shown in Figure 2 or Figure 3, polypeptides consisting of about amino acid 40 to about amino acid 50 of a 109P1 D4 protein shown in Figure 2 or Figure 3, polypeptides consisting of about amino acid 50 to about amino acid 60 of a 109P1 D4 protein shown in Figure 2 or Figure 3, polypeptides consisting of about amino acid 60 to about amino acid 70 of a 109P1 D4 protein shown in Figure 2 or Figure 3, polypeptides consisting of about amino acid 70 to about amino acid 80 of a 109P1 D4 protein shown in Figure 2 or Figure 3, polypeptides consisting of about amino acid 80 to about amino acid 90 of a 109P1 D4 protein shown in Figure 2 or Figure 3, polypeptides consisting of about amino acid 90 to about amino acid 100 of a 109P1D4 protein shown in Figure 2 or Figure 3, etc. throughout the entirety of a 109P1 D4 amino acid sequence. Moreover, polypeptides consisting of about amino acid 1 (or 20 or 30 or 40 etc.) to about amino acid 20, (or 130, or 140 or 150 etc.) of a 109P1D4 protein shown in Figure 2 or Figure 3 are embodiments of the invention. It is to be appreciated that the starting and stopping positions in this paragraph refer to the specified position as well as that position plus or minus 5 residues.

109P1 D4-related proteins are generated using standard peptide synthesis technology or using chemical cleavage methods well known in the art. Alternatively, recombinant methods can be used to generate nucleic acid molecules that encode a 109P1 D4-related protein. In one embodiment, nucleic acid molecules provide a means to generate defined fragments of a 109P1 D4 protein (or variants, homologs or analogs thereof).

III. A. L Motif-bearing Protein Embodiments Additional illustrative embodiments of the invention disclosed herein include 109PI D4 polypeptides comprising the amino acid residues of one or more of the biological motifs contained within a 109P1 D4 polypeptide sequence set forth in Figure 2 or Figure 3. Various motifs are known in the art, and a protein can be evaluated for the presence of such motifs by a number of publicly available Internet sites (see, e. g., URL addresses : pfam. wustl. edu/; searchlauncher. bcm. tmc. edu/seq- search/struc-predict. htmt ; psort. ims. u-tokyo. ac. jpl ; cbs. dtu. dk/ ; ebi. ac. uk/interpro/scan. html ; expasy. ch/toolslscnpsit1. html ; Epimatrix and Eimer, Brown University, brown. edu/Research/TB-HIV_Lab/epimatrixlepimatrix. html ; and BIMAS, bimas. dcrt. nih. gov/.).

Motif bearing subsequences of all 109P1 D4 variant proteins are set forth and identified in Tables ViIl-XXI and XXII- XLIX.

Table V sets forth several frequently occurring motifs based on pfam searches (see URL address pfam. wustl. edu/).

The columns of Table V list (1) motif name abbreviation, (2) percent identity found amongst the different member of the motif family, (3) motif name or description and (4) most common function ; location information is included if the motif is relevant for location.

Polypeptides comprising one or more of the 109P1 D4 motifs discussed above are useful in elucidating the specific characteristics of a malignant phenotype in view of the observation that the 109P1 D4 motifs discussed above are associated with growth dysregulation and because 109P1D4 is overexpressed in certain cancers (See, e. g., Table 1). Casein kinase ll, cAMP and camp-dependent protein kinase, and Protein Kinase C, for example, are enzymes known to be associated with the development of the malignant phenotype (see e. g. Chen et a/., Lab Invest., 78 (2) : 165-174 (1998) ; Gaiddon et a/., Endocrinology 136 (10) : 4331-4338 (1995) ; Hall et al., Nucleic Acids Research 24 (6) : 1119-1126 (1996) ; Peterziel eta/., Oncogene 18 (46) : 6322-6329 (1999) and O'Brian, Oncol. Rep. 5 (2) : 305-309 (1998)). Moreover, both glycosylation and myristoylation are protein modifications also associated with cancer and cancer progression (see e. g. Dennis et al., Biochem.

Biophys. Acta 1473 (1) : 21-34 (1999) ; Raju et a/., Exp. Cell Res. 235 (1) : 145-154 (1997)). Amidation is another protein modification also associated with cancer and cancer progression (see e. g. Treston et aL, J. Natl. Cancer Inst. Monogr. (13) : 169-175 (1992)).

In another embodiment, proteins of the invention comprise one or more of the immunoreactive epitopes identified in accordance with art-accepted methods, such as the peptides set forth in Tables VIII-XXI and XXll-XLlX. CTL epitopes can be determined using specific algorithms to identify peptides within a 109P1D4 protein that are capable of optimally binding to specified HLA alleles (e. g., Table IV ; Epimatrix and Eimer, Brown University, URL brown. edu/Research/TB- HlV_Lablepimatrix/epimatrix. html ; and BIMAS, URL bimas. dcrt. nih. gov/.) Moreover, processes for identifying peptides that have sufficient binding affinity for HLA molecules and which are correlated with being immunogenic epitopes, are well known in the art, and are carried out without undue experimentation. In addition, processes for identifying peptides that are immunogenic epitopes, are well known in the art, and are carried out without undue experimentation either in vitro or in vivo.

Also known in the art are principles for creating analogs of such epitopes in order to modulate immunogenicity. For example, one begins with an epitope that bears a CTL or HTL motif (see, e. g., the HLA Class I and HLA Class II motifs/supermotifs of Table IV). The epitope is analoge by substituting out an amino acid at one of the specified positions, and replacing it with another amino acid specified for that position. For example, on the basis of residues defined in Table IV, one can substitute out a deleterious residue in favor of any other residue, such as a preferred residue ; substitute a less- preferred residue with a preferred residue ; or substitute an originally-occurring preferred residue with another preferred residue. Substitutions can occur at primary anchor positions or at other positions in a peptide ; see,, e. g., Table IV.

A variety of references reflect the art regarding the identification and generation of epitopes in a protein of interest as well as analogs thereof. See, for example, WO 97/33602 to Chesnut et al. ; Sette, Immunogenetics 1999 50 (3-4) : 201- 212 ; Sette et al., J. lmmunol. 2001166 (2) : 1389-1397 ; Sidneyeta/., Hum. Immunol. 199758 (1) : 12-20 ; Kondo et al., Immunogenetics 1997 45 (4) : 249-258 ; Sidney et al., J. Immunol. 1996 157 (8) : 3480-90 ; and Falk et al., Nature 351 : 290-6 (1991) ; Hunt et al., Science 255 : 1261-3 (1992) ; Parker et al., J. Immunol. 149 : 3580-7 (1992) ; Parker et al., J. Immunol.

152 : 163-75 (1994)) ; Kast et al., 1994152 (8) : 3904-12 ; Borras-Cuesta et a/., Hum. Immunol. 2000 61 (3) : 266-278 ; Alexander et aL, J. Immunol. 2000 164 (3) ; 164 (3) : 1625-1633 ; Alexander et al., PMID : 7895164, Ul : 95202582 ; O'Sullivan et al., J.

Immunol. 1991 147 (8) : 2663-2669 ; Alexander era/., immunity 19941 (9) : 751-761 and Alexander et al., Immunol. Res. 1998 18 (2) : 79-92.

Related embodiments of the invention include polypeptides comprising combinations of the different motifs set forth in Table VI, and/or, one or more of the predicted CTL epitopes of Tables VIII-XXI and XXII-XLIX, and/or, one or more of the predicted HTL epitopes of Tables XLVI-XLIX, and/or, one or more of the T cell binding motifs known in the art. Preferred embodiments contain no insertions, deletions or substitutions either within the motifs or within the intervening sequences of the polypeptides. In addition, embodiments which include a number of either N-terminal and/or C-terminal amino acid residues on either side of these motifs may be desirable (to, for example, include a greater portion of the polypeptide architecture in which the motif is located). Typically, the number of N-terminal and/or C-terminal amino acid residues on either side of a motif is between about 1 to about 100 amino acid residues, preferably 5 to about 50 amino acid residues.

109P1 D4-related proteins are embodied in many forms, preferably in isolated form. A purified 109P1 D4 protein molecule will be substantially free of other proteins or molecules that impair the binding of 109P1 D4 to antibody, T cell or other ligand. The nature and degree of isolation and purification will depend on the intended use. Embodiments of a 109P1 D4- related proteins include purified 109P1D4-related proteins and functional, soluble 109P1D4-related proteins. ! n one embodiment, a functional, soluble 109P1D4 protein or fragment thereof retains the ability to be bound by antibody, T cell or other ligand.

The invention also provides 109P1 D4 proteins comprising biologically active fragments of a 109P1 D4 amino acid sequence shown in Figure 2 or Figure 3. Such proteins exhibit properties of the starting 109P1 D4 protein, such as the ability to elicit the generation of antibodies that specifically bind an epitope associated with the starting 109P1 D4 protein ; to be bound by such antibodies ; to elicit the activation of HTL or CTL ; and/or, to be recognized by HTL or CTL that also specifically bind to the starting protein.

109P1 D4-related polypeptides that contain particularly interesting structures can be predicted and/or identified using various analytical techniques well known in the art, including, for example, the methods of Chou-Fasman, Garnier-Robson, kyste- Doolittle, Eisenberg, Karplus-Schultz or Jameson-Wolf analysis, or based on immunogenicity. Fragments that contain such structures are particularly useful in generating subunit-specific anti-109P1 D4 antibodies or T cells or in identifying cellular factors that bind to 109P1 D4. For example, hydrophilicity profiles can be generated, and immunogenic peptide fragments identified, using the method of Hopp, T. P. and Woods, K. R., 1981, Proc. Natl. Acad. Sci. U, S. A. 78 : 3824-3828. Hydropathicity profiles can be generated, and immunogenic peptide fragments identified, using the method of Kyte, J. and Doolittle, R. F., 1982, J.

Mol. Biol. 157 : 105-132. Percent (%) Accessible Residues profiles can be generated, and immunogenic peptide fragments identified, using the method of Janin J., 1979, Nature 277 : 491-492. Average Flexibility profiles can be generated, and immunogenic peptide fragments identified, using the method of Bhaskaran R., Ponnuswamy P. K., 1988, Int. J. Pept. Protein Res. 32 : 242-255. Beta-turn profiles can be generated, and immunogenic peptide fragments identified, using the method of Deleage, G., Roux B., 1987, Protein Engineering 1 : 289-294.

CTL epitopes can be determined using specific algorithms to identify peptides within a 109P1 D4 protein that are capable of optimally binding to specified HLA alleles (e. g., by using the SYFPEITHI site at World Wide Web URL syfpeithi. bmi- heidelberg. com/; the listings in Table IV (A)- (E) ; Epimatri) Jm and Eimer, Brown University, URL (brown. edu/Research/TB- HlVlab/epimatrixlepimatrix. html) ; and BiMAS, URL bimas. dcrt. nih. gov/). Illustrating this, peptide epitopes from 109P1D4 that are presented in the context of human MHC Class I molecules, e. g., HLA-A1, A2, A3, A11, A24, B7 and B35 were predicted (see, e. g., Tables VIII-XXI, XXII-XLIX). Specifically, the complete amino acid sequence of the 109P1D4 protein and relevant portions of other variants, i. e., for HLA Class I predictions 9 flanking residues on either side of a point mutation or exon juction, and for HLA Class II predictions 14 flanking residues on either side of a point mutation or exon junction corresponding to that variant, were entered into the HLA Peptide Motif Search algorithm found in the Bioinformatics and Molecular Analysis Section (BIMAS) web site listed above ; in addition to the site SYFPEITHI, at URL syfpeithi. bmi- heidelberg. com/.

The HLA peptide motif search algorithm was developed by Dr. Ken Parker based on binding of specific peptide sequences in the groove of HLA Class I molecules, in particular HLA-A2 (see, e. g., Falk eta/., Nature 351 : 290-6 (1991) ; Hunt et a/., Science 255 : 1261-3 (1992) ; Parker et al., J. Immunol. 149 : 3580-7 (1992) ; Parker et al., J. Immunol. 152 : 163-75 (1994)). This algorithm allows location and ranking of 8-mer, 9-mer, and 10-mer peptides from a complete protein sequence for predicted binding to HLA-A2 as well as numerous other HLA Class I molecules. Many HLA class I binding peptides are 8-, 9-, 10 or 11-mers. For example, for Class I HLA-A2, the epitopes preferably contain a leucine (L) or methionine (M) at position 2 and a valine (V) or leucine (L) at the C-terminus (see, e. g., Parker et al., J. Immunol. 149 : 3580-7 (1992)).

Selected results of 109P1D4 predicted binding peptides are shown in Tables VIII-XXI and XXII-XLIX herein. ln Tables Vlil- XXI and XXII-XLVII, selected candidates, 9-mers and 10-mers, for each family member are shown along with their location, the amino acid sequence of each specific peptide, and an estimated binding score. In Tables XLVI-XLIX, selected candidates, 15-mers, for each family member are shown along with their location, the amino acid sequence of each specific peptide, and an estimated binding score. The binding score corresponds to the estimated half time of dissociation of complexes containing the peptide at 370C at pH 6. 5. Peptides with the highest binding score are predicted to be the most tightly bound to HLA Class I on the cell surface for the greatest period of time and thus represent the best immunogenic targets for T-cell recognition.

Actual binding of peptides to an HLA allele can be evaluated by stabilization of HLA expression on the antigen- processing defective cell line T2 (see, e. g., Xue eta/., Prostate 30 : 73-8 (1997) and Peshwa etal., Prostate 36 : 129-38 (1998)). immunogenicity of specific peptides can be evaluated in vitro by stimulation of CD8+ cytotoxic T lymphocytes (CTL) in the presence of antigen presenting cells such as dendritic cells.

It is to be appreciated that every epitope predicted by the BIMAS site, EpimerTM and Epimatrix sites, or specified by the HLA class I or class II motifs available in the art or which become part of the art such as set forth in Table IV (or determined using World Wide Web site URL syfpeithi. bmi-heidelberg. com/, or BIMAS, bimas. dcrt. nih. gov/) are to be"applied" to a 109P1D4 protein in accordance with the invention. As used in this context"applied"means that a 109P1D4 protein is evaluated, e. g., visually or by computer-based patterns finding methods, as appreciated by those of skill in the relevant art.

Every subsequence of a 109P1D4 protein of 8, 9, 10, or 11 amino acid residues that bears an HLA Class I motif, or a subsequence of 9 or more amino acid residues that bear an HLA Class II motif are within the scope of the invention.

III. B.) Expression of 109P1D4-related Proteins In an embodiment described in the examples that follow, 109P1 D4 can be conveniently expressed in cells (such as 293T cells) transfected with a commercially available expression vector such as a CMV-driven expression vector encoding 109P1D4 with a C-terminal 6XHis and MYC tag (pcDNA3. 1/mycHIS, lnvitrogen or Tag5, GenHunter Corporation, Nashville TN). The Tag5 vector provides an lgGK secretion signal that can be used to facilitate the production of a secreted 109P1 D4 protein in transfected cells. The secreted HIS-tagged 109PI D4 in the culture media can be purified, e. g., using a nickel column using standard techniques.

Ill. C.) Modifications of 109P1D4-related Proteins Modifications of 109P1 D4-related proteins such as covalent modifications are included within the scope of this invention. One type of covalent modification includes reacting targeted amino acid residues of a 109P1 D4 polypeptide with an organic derivatizing agent that is capable of reacting with selected side chains or the N-or C-terminal residues of a 109P1 D4 protein. Another type of covalent modification of a 109P1 D4 polypeptide included within the scope of this invention comprises altering the native glycosylation pattern of a protein of the invention. Another type of covalent modification of 109P1D4 comprises linking a 109PI D4 polypeptide to one of a variety of nonproteinaceous polymers, e. g., polyethylene glycol (PEG), polypropylene glycol, or polyoxyalkylenes, in the manner set forth in U. S. Patent Nos. 4, 640, 835 ; 4, 496, 689 ; 4, 301, 144 ; 4, 670, 417 ; 4, 791, 192 or 4, 179, 337.

The 109P1 D4-related proteins of the present invention can also be modified to form a chimeric molecule comprising 109P1D4 fused to another, heterologous polypeptide or amino acid sequence. Such a chimeric molecule can be synthesized chemically or recombinantly. A chimeric molecule can have a protein of the invention fused to another tumor- associated antigen or fragment thereof. Alternatively, a protein in accordance with the invention can comprise a fusion of fragments of a 109P1D4 sequence (amino or nucleic acid) such that a molecule is created that is not, through its length, directly homologous to the amino or nucleic acid sequences shown in Figure 2 or Figure 3. Such a chimeric molecule can comprise multiples of the same subsequence of 109P1D4. A chimeric molecule can comprise a fusion of a 109P1D4-related protein with a polyhistidine epitope tag, which provides an epitope to which immobilized nickel can selectively bind, with cytokines or with growth factors. The epitope tag is generally placed at the amino-or carboxyl-terminus of a 109P1 D4 protein. In an alternative embodiment, the chimeric molecule can comprise a fusion of a 109P1 D4-related protein with an immunoglobulin or a particular region of an immunoglobulin. For a bivalent form of the chimeric molecule (also referred to as an"immunoadhesin"), such a fusion could be to the Fc region of an IgG molecule. The Ig fusions preferably include the substitution of a soluble (transmembrane domain deleted or inactivated) form of a 109P1D4 polypeptide in place of at least one variable region within an Ig molecule. In a preferred embodiment, the immunoglobulin fusion includes the hinge, CH2 and CH3, or the hinge, CHI, CH2 and CH3 regions of an IgGI molecule. For the production of immunoglobulin fusions see, e. g., U. S. Patent No. 5, 428, 130 issued June 27, 1995.

III. D.) Uses of 109P1D4-related Proteins The proteins of the invention have a number of different specific uses. As 109P1 D4 is highly expressed in prostate and other cancers, 109P1 D4-related proteins are used in methods that assess the status of 109P1D4 gene products in normal versus cancerous tissues, thereby elucidating the malignant phenotype. Typically, polypeptides from specific regions of a 109P1D4 protein are used to assess the presence of perturbations (such as deletions, insertions, point mutations etc.) in those regions (such as regions containing one or more motifs). Exemplary assays utilize antibodies or T cells targeting 109P1 D4-related proteins comprising the amino acid residues of one or more of the biological motifs contained within a 109P1 D4 polypeptide sequence in order to evaluate the characteristics of this region in normal versus cancerous tissues or to elicit an immune response to the epitope. Alternatively, 1 O9P1 D4-related proteins that contain the amino acid residues of one or more of the biological motifs in a 109P1 D4 protein are used to screen for factors that interact with that region of 109P1D4.

109P1D4 protein fragments/subsequences are particularly useful in generating and characterizing domain-specific antibodies (e. g., antibodies recognizing an extracellular or intracellular epitope of a 109P1 D4 protein), for identifying agents or cellular factors that bind to 109P1 D4 or a particular structural domain thereof, and in various therapeutic and diagnostic contexts, including but not limited to diagnostic assays, cancer vaccines and methods of preparing such vaccines.

Proteins encoded by the 109P1 D4 genes, or by analogs, homologs or fragments thereof, have a variety of uses, including but not limited to generating antibodies and in methods for identifying ligands and other agents and cellular constituents that bind to a 109P1D4 gene product. Antibodies raised against a 109P1D4 protein or fragment thereof are useful in diagnostic and prognostic assays, and imaging methodologies in the management of human cancers characterized by expression of 109P1D4 protein, such as those listed in Table I. Such antibodies can be expressed intracellularly and used in methods of treating patients with such cancers. 109P1 D4-related nucleic acids or proteins are also used in generating HTL or CTL responses.

Various immunological assays useful for the detection of 109P1 D4 proteins are used, including but not limited to various types of radioimmunoassays, enzyme-linked immunosorbent assays (ELISA), enzyme-linked immunofluorescent assays (ELIFA), immunocytochemical methods, and the like. Antibodies can be labeled and used as immunological imaging reagents capable of detecting 109P1D4-expressing cells (e. g., in radioscintigraphic imaging methods). 109P1D4 proteins are also particularly useful in generating cancer vaccines, as further described herein.

IV.) 109P1D4Antibodies Another aspect of the invention provides antibodies that bind to 109P1 D4-related proteins. Preferred antibodies specifically bind to a 109P1 D4-related protein and do not bind (or bind weakly) to peptides or proteins that are not 109P1 D4- related proteins under physiological conditions. In this context, examples of physiological conditions include : 1) phosphate buffered saline ; 2) Tris-buffered saline containing 25mM Tris and 150 mM NaCl ; or normal saline (0. 9% NaCI) ; 4) animal serum such as human serum ; or, 5) a combination of any of 1) through 4) ; these reactions preferably taking place at pH 7. 5, alternatively in a range of pH 7. 0 to 8. 0, or alternatively in a range of pH 6. 5 to 8. 5 ; also, these reactions taking place at a temperature between 4°C to 37°C. For example, antibodies that bind 109P1 D4 can bind 109P1 D4-related proteins such as the homologs or analogs thereof.

109P1 D4 antibodies of the invention are particularly useful in cancer (see, e. g., Table I) diagnostic and prognostic assays, and imaging methodologies. Similarly, such antibodies are useful in the treatment, diagnosis, and/or prognosis of other cancers, to the extent 109P1 D4 is also expressed or overexpressed in these other cancers. Moreover, intracellularly expressed antibodies (e. g., single chain antibodies) are therapeutical useful in treating cancers in which the expression of 109P1 D4 is involved, such as advanced or metastatic prostate cancers.

The invention also provides various immunological assays useful for the detection and quantification of 109P1 D4 and mutant 109P1 D4-related proteins. Such assays can comprise one or more 109P1 D4 antibodies capable of recognizing and binding a 109P1 D4-related protein, as appropriate. These assays are performed within various immunological assay formats well known in the art, including but not limited to various types of radioimmunoassays, enzyme-linked immunosorbent assays (ELISA), enzyme-linked immunofluorescent assays (ELIFA), and the like.

Immunological non-antibody assays of the invention also comprise T cell immunogenicity assays (inhibitory or stimulatory) as well as major histocompatibility complex (MHC) binding assays.

In addition, immunological imaging methods capable of detecting prostate cancer and other cancers expressing 109P1 D4 are also provided by the invention, including but not limited to radioscinEgraphic imaging methods using labeled 109P1 D4 antibodies. Such assays are clinically useful in the detection, monitoring, and prognosis of 109P1 D4 expressing cancers such as prostate cancer.

109P1 D4 antibodies are also used in methods for purifying a 109P1 D4-related protein and for isolating 109P1 D4 homologues and related molecules. For example, a method of purifying a 109P1 D4-related protein comprises incubating a 109P1 D4 antibody, which has been coupled to a solid matrix, with a lysate or other solution containing a 109P1 D4-related protein under conditions that permit the 109P1 D4 antibody to bind to the 109P1 D4-related protein ; washing the solid matrix to eliminate impurities ; and eluting the 109P1D4-related protein from the coupled antibody. Other uses of 109P1 D4 antibodies in accordance with the invention include generating anti-idiotypic antibodies that mimic a 109P1 D4 protein.

Various methods for the preparation of antibodies are well known in the art. For example, antibodies can be prepared by immunizing a suitable mammalian host using a 109P1 D4-related protein, peptide, or fragment, in isolated or immunoconjugated form (Antibodies : A Laboratory Manual, CSH Press, Eds., Harlow, and Lane (1988) ; Harlow, Antibodies, Cold Spring Harbor Press, NY (1989)). In addition, fusion proteins of 109P1D4 can also be used, such as a 109P1 D4 GST-fusion protein. In a particular embodiment, a GST fusion protein comprising all or most of the amino acid sequence of Figure 2 or Figure 3 is produced, then used as an immunogen to generate appropriate antibodies. In another embodiment, a 109P1D4-related protein is synthesized and used as an immunogen. in addition, naked DNA immunization techniques known in the art are used (with or without purified 109P1 D4-related protein or 109P1 D4 expressing cells) to generate an immune response to the encoded immunogen (for review, see Donnelly et al., 1997, Ann. Rev. Immunol. 15 : 617-648).

The amino acid sequence of a 109P1 D4 protein as shown in Figure 2 or Figure 3 can be analyzed to select specific regions of the 109P1 D4 protein for generating antibodies. For example, hydrophobicity and hydrophilicity analyses of a 109P1 D4 amino acid sequence are used to identify hydrophilic regions in the 109P1D4 structure. Regions of a 109P1D4 protein that show immunogenic structure, as well as other regions and domains, can readily be identified using various other methods known in the art, such as Chou-Fasman, Garnier-Robson, Kyte-Doolittle, Eisenberg, Karplus-Schultz or Jameson-Wolf analysis. Hydrophilicity profiles can be generated using the method of Hopp, T. P. and Woods, K. R., 1981, Proc. Natl. Acad. Sci. U. S. A. 78 : 3824- 3828. Hydropathicity profiles can be generated using the method of Kyte, J. and Doolittle, R. F., 1982, J. Mol. Biol. 157 : 105- 132. Percent (%) Accessible Residues profiles can be generated using the method of Janin J., 1979, Nature 277 : 491-492.

Average Flexibility profiles can be generated using the method of Bhaskaran R., Ponnuswamy P. K., 1988, Int. J. Pept.

Protein Res. 32 : 242-255. Beta-turn profiles can be generated using the method of Deleage, G., Roux B., 1987, Protein Engineering 1 : 289-294. Thus, each region identified by any of these programs or methods is within the scope of the present invention. Methods for the generation of 109P1 D4 antibodies are further illustrated by way of the examples provided herein.

Methods for preparing a protein or polypeptide for use as an immunogen are we ! i known in the art. Also well known in the art are methods for preparing immunogenic conjugates of a protein with a carrier, such as BSA, KLH or other carrier protein. In some circumstances, direct conjugation using, for example, carbodiimide reagents are used ; in other instances linking reagents such as those supplied by Pierce Chemical Co., Rockford, IL, are effective. Administration of a 109P1D4 immunogen is often conducted by injection over a suitable time period and with use of a suitable adjuvant, as is understood in the art. During the immunization schdule, titers of antibodies can be taken to determine adequacy of antibody formation.

109P1 D4 monoclonal antibodies can be produced by various means well known in the art. For example, immortalized cell lines that secrete a desired monoclonal antibody are prepared using the standard hybridoma technology of Kohler and Milstein or modifications that immortalize antibody-producing B cells, as is generally known. Immortalized cell lines that secrete the desired antibodies are screened by immunoassay in which the antigen is a 109P1D4-related protein. When the appropriate immortalized cell culture is identified, the cells can be expanded and antibodies produced either from in vitro cultures or from ascites fluid.

The antibodies or fragments of the invention can also be produced, by recombinant means. Regions that bind specifically to the desired regions of a 109P1 D4 protein can also be produced in the context of chimeric or complementarity- determining region (CDR) grafted antibodies of multiple species origin. Humanized or human 109P1 D4 antibodies can also be produced, and are preferred for use in therapeutic contexts. Methods for humanizing murine and other non-human antibodies, by substituting one or more of the non-human antibody CDRs for corresponding human antibody sequences, are well known (see for example, Jones et al., 1986, Nature 321 : 522-525 ; Riechmann et al., 1988, Nature 332 : 323-327 ; Verhoeyen et al., 1988, Science 239 : 1534-1536). See also, Carter et al., 1993, Proc. Nat). Acad. Sci. USA 89 : 4285 and Sims etal., 1993, J. immune). 151 : 2296.

Methods for producing fully human monoclonal antibodies include phage display and transgenic methods (for review, see Vaughan et al., 1998, Nature Biotechnology 16 : 535-539). Fully human 109P1 D4 monoclonal antibodies can be generated using cloning technologies employing large human lg gene combinatorial libraries (i. e., phage display) (Griffiths and Hoogenboom, Building an in vitro immune system : human antibodies from phage display libraries. In : Protein Engineering of Antibody Molecules for Prophylactic and Therapeutic Applications in Man, Clark, M. (Ed.), Nottingham Academic, pp 45-64 (1993) ; Burton and Barbas, Human Antibodies from combinatorial libraries. nid., pp 65-82). Fully human 109P1 D4 monoclonal antibodies can also be produced using transgenic mice engineered to contain human immunoglobulin gene loci as described in PCT Patent Application W098/24893, Kucherlapati and Jakobovits et al., published December 3, 1997 (see also, Jakobovits, 1998, Exp. Opin. Invest.

Drugs 7 (4) : 607-614 ; U. S. patents 6, 162, 963 issued 19 December 2000 ; 6, 150, 584 issued 12 November 2000 ; and, 6, 114598 issued 5 September 2000). This method avoids the in vitro manipulation required with phage display technology and efficiently produces high affinity authentic human antibodies.

Reactivity of 109P1 D4 antibodies with a 109P1 D4-related protein can be established by a number of well known means, including Western blot, immunoprecipitation, ELISA, and FACS analyses using, as appropriate, 109P1 D4-related proteins, 109P1 D4-expressing cells or extracts thereof. A 109P1 D4 antibody or fragment thereof can be labeled with a detectable marker or conjugated to a second molecule. Suitable detectable markers include, but are not limited to, a radioisotope, a fluorescent compound, a bioluminescent compound, chemiluminescent compound, a metal chelator or an enzyme. Further, bi-specific antibodies specific for two or more 109P1 D4 epitopes are generated using methods generally known in the art. Homodimeric antibodies can also be generated by cross-linking techniques known in the art (e. g., Wolf et a/., Cancer Res. 53 : 2560-2565).

V.) 109P1 D4 Ce)) u) ar immune Responses The mechanism by which T cells recognize antigens has been delineated. Efficacious peptide epitope vaccine compositions of the invention induce a therapeutic or prophylactic immune responses in very broad segments of the world- wide population. For an understanding of the value and efficacy of compositions of the invention that induce cellular immune responses, a brief review of immunology-related technology is provided.

A complex of an HLA molecule and a peptidic antigen acts as the ligand recognized by HLA-restricted T cells (Buus, S. et al., Ce1147 : 1071, 1986 ; Babbitt, B. P. et al., Nature 317 : 359, 1985 ; Townsend, A. and Bodmer, H., Annu. Rev.

Immunol. 7 : 601, 1989 ; Germain, R. N., Annu. Rev. Immunol. 11 : 403, 1993). Through the study of single amino acid substituted antigen analogs and the sequencing of endogenously bound, naturally processed peptides, critical residues that correspond to motifs required for specific binding to HLA antigen molecules have been identified and are set forth in Table IV (see also, e. g., Southwood, et al., J. Immunol. 160 : 3363, 1998 ; Rammensee, et al. l Immunogenetics 41 : 178, 1995 ; Rammensee et a., SYFPEITHI, access via World Wide Web at URL (134. 2. 96. 221/scripts. hlaserver. dll/home. htm) ; Sette, A. and Sidney, J. Curr. Opin. Immunol. 10 : 478, 1998 ; Engelhard, V. H., Curr. Opin. Immunol. 6 : 13, 1994 ; Sette, A. and Grey, H.

M., Curr. Opin. Immunol. 4 : 79, 1992 ; Sinigaglia, F. and Hammer, J. Curr. Biol. 6 : 52, 1994 ; Ruppert et al., Cell 74 : 929-937, 1993 ; Kondo et al., J. Immunol. 155 : 4307-4312, 1995 ; Sidney et al., J. Immunol. 157 : 3480-3490, 1996 ; Sidney et al., Human Immunol. 45 : 79-93, 1996 ; Sette, A. and Sidney, J. Immunogenetics 1999 Nov; 50(3-4):201-12, Review).

Furthermore, x-ray crystallographic analyses of HLA-peptide complexes have revealed pockets within the peptide binding cleft/groove of HLA molecules which accommodate, in an allele-specific mode, residues borne by peptide ligands ; these residues in turn determine the HLA binding capacity of the peptides in which they are present. (See, e. g., Madden, D. R. Annu. Rev. Immunol. 13 : 587, 1995 ; Smith, et al., Immunity4 : 203, 1996 ; Fremont et al., Immunity 8 : 305, 1998 ; Stern et al., Structure 2 : 245, 1994 ; Jones, E. Y. Curr. Opin. Immunol. 9 : 75, 1997 ; Brown, J. H. et al., Nature 364 : 33, 1993 ; Guo, H. C. et aL, Proc. Natl. Acad. Sci. USA 90 : 8053, 1993 ; Guo, H. C. et al., Nature 360 : 364, 1992 ; Silver, M. L. et al., Nature 360 : 367, 1992 ; Matsumura, M. et al., Science 257 : 927, 1992 ; Madden era/., Ce//70 : 1035, 1992 ; Fremont, D. H. et al., Science 257 : 919, 1992 ; Saper, M. A., Bjorkman, P. J. and Wiley, D. C., J. Mol. Biol. 219 : 277, 1991.) Accordingly, the definition of class I and class II allele-specific HLA binding motifs, or class I or class 11 supermotifs allows identification of regions within a protein that are correlated with binding to particular HLA antigen (s).

Thus, by a process of HLA motif identification, candidates for epitope-based vaccines have been identified ; such candidates can be further evaluated by HLA-peptide binding assays to determine binding affinity and/or the time period of association of the epitope and its corresponding HLA molecule. Additional confirmatory work can be performed to select, amongst these vaccine candidates, epitopes with preferred characteristics in terms of population coverage, and/or immunogenicity.

Various strategies can be utilized to evaluate cellular immunogenicity, including : 1) Evaluation of primary T cell cultures from normal individuals (see, e. g., Wentworth, P. A. et al., Mol. Immunol.

32 : 603, 1995 ; Celis, E. etal., Proc. Natl. Acad. Sci. USA 91 : 2105, 1994 ; Tsai, V. et al., J. Immunol. 158 : 1796, 1997 ; Kawashima, 1. et aL, Human Immunol. 59 : 1, 1998). This procedure involves the stimulation of peripheral blood lymphocytes (PBL) from normal subjects with a test peptide in the presence of antigen presenting cells in vitro over a period of several weeks. T cells specific for the peptide become activated during this time and are detected using, e. g., a lymphokine-or 51 Cr-release assay involving peptide sensitized target cells.

2) immunization of HLA transgenic mice (see, e. g., Wentworth, P. A. et al., J. Immunol. 2697, 1996 ; Wentworth, P.

A. et al., Int. lmmunol. 8 : 651, 1996 ; Alexander, J. et al., J. Immunol. 159 : 4753, 1997). For example, in such methods peptides in incomplete Freund's adjuvant are administered subcutaneously to HLA transgenic mice. Several weeks following immunization, splenocytes are removed and cultured in vitro in the presence of test peptide for approximately one week.

Peptide-specific T cells are detected using, e. g., a 51 Cr-release assay involving peptide sensitized target cells and target cells expressing endogenously generated antigen.

3) Demonstration of recall T cell responses from immune individuals who have been either effectively vaccinated and/or from chronically ill patients (see, e. g., Rehermann, B. et al., J. Exp. Med. 181 : 1047, 1995 ; Doolan, D. L. et al, Immunity 7 : 97, 1997 ; Bertoni, iR. et al., J. Clin. Invest. 100 : 503, 1997 ; Threlkeld, S. C. et al, J. Immunol 159 : 1648, 1997 ; Diepolder, H. M. et al, J. ViroL 71 : 6011, 1997). Accordingly, recall responses are detected by culturing PBL from subjects that have been exposed to the antigen due to disease and thus have generated an immune response"naturally", or from patients who were vaccinated against the antigen. PBL from subjects are cultured in vitro for 1-2 weeks in the presence of test peptide plus antigen presenting cells (APC) to allow activation of"memory"T cells, as compared to"naive"T cells. At the end of the culture period, T cell activity is detected using assays including 51 Cr release involving peptide-sensitized targets, T cell proliferation, or lymphokine release.

Vl.) 109P1D4 Transgenic Animals Nucleic acids that encode a 109P1D4-related protein can also be used to generate either transgenic animals or "knock out"animals that, in turn, are useful in the development and screening of therapeutically useful reagents. In accordance with established techniques, cDNA encoding 109P1 D4 can be used to clone genomic DNA that encodes 109P1D4. The cloned genomic sequences can then be used to generate transgenic animals containing cells that express DNA that encode 109P1 D4. Methods for generating transgenic animals, particularly animals such as mice or rats, have become conventional in the art and are described, for example, in U. S. Patent Nos. 4, 736, 866 issued 12 April 1988, and 4, 870, 009 issued 26 September 1989. Typically, particular cells would be targeted for 109P1 D4 transgene incorporation with tissue-specific enhancers.

Transgenic animals that include a copy of a transgene encoding 109P1 D4 can be used to examine the effect of increased expression of DNA that encodes 109P1 D4. Such animals can be used as tester animals for reagents thought to confer protection from, for example, pathological conditions associated with its overexpression. In accordance with this aspect of the invention, an animal is treated with a reagent and a reduced incidence of a pathological condition, compared to untreated animals that bear the transgene, would indicate a potential therapeutic intervention for the pathological condition.

Alternatively, non-human homologues of 109P1 D4 can be used to construct a 109P1 D4"knock out"animal that has a defective or altered gene encoding 109P1 D4 as a result of homologous recombination between the endogenous gene encoding 109P1 D4 and altered genomic DNA encoding 109P1 D4 introduced into an embryonic cell of the animal. For example, cDNA that encodes 109P1 D4 can be used to clone genomic DNA encoding 109P1 D4 in accordance with established techniques. A portion of the genomic DNA encoding 109P1 D4 can be deleted or replaced with another gene, such as a gene encoding a selectable marker that can be used to monitor integration. Typically, several kilobases of unaltered flanking DNA (both at the 5'and 3'ends) are included in the vector (see, e. g., Thomas and Capecchi, Cell, 51 : 503 (1987) for a description of homologous recombination vectors). The vector is introduced into an embryonic stem cell line (e. g., by electroporation) and cells in which the introduced DNA has homologously recombined with the endogenous DNA are selected (see, e. g., Li et al., Cell, 69 : 915 (1992)). The selected cells are then injected into a blastocyst of an animal (e. g., a mouse or rat) to form aggregation chimeras (see, e. g., Bradley, in Teratocarcinomas and Embryonic Stem Cells : A Practical Approach, E. J. Robertson, ed. (IRL, Oxford, 1987), pp. 113-152). A chimeric embryo can then be implanted into a suitable pseudopregnant female foster animal, and the embryo brought to term to create a"knock out"animal. Progeny harboring the homologously recombined DNA in their germ cells can be identified by standard techniques and used to breed animals in which all cells of the animal contain the homologously recombined DNA. Knock out animals can be characterized, for example, for their ability to defend against certain pathological conditions or for their development of pathological conditions due to absence of a 109P1 D4 polypeptide.

Vll.) Methods forthe Detection of 109PI D4 Another aspect of the present invention relates to methods for detecting 109P1D4 polynucleotides and 109P1D4- related proteins, as well as methods for identifying a cell that expresses 109P1 D4. The expression profile of 109P1 D4 makes it a diagnostic marker for metastasized disease. Accordingly, the status of 109P1 D4 gene products provides information useful for predicting a variety of factors including susceptibility to advanced stage disease, rate of progression, and/or tumor aggressiveness. As discussed in detail herein, the status of 109P1D4 gene products in patient samples can be analyzed by a variety protocols that are well known in the art including immunohistochemical analysis, the variety of Northern blotting techniques including in situ hybridization, RT-PCR analysis (for example on laser capture micro-dissected samples), Western blot analysis and tissue array analysis.

More particularly, the invention provides assays for the detection of 109P1 D4 polynucleotides in a biological sample, such as serum, bone, prostate, and other tissues, urine, semen, cell preparations, and the like. Detectable 109P1D4 polynucleotides include, for example, a 109P1 D4 gene or fragment thereof, 109P1 D4 mRNA, alternative splice variant 109P1 D4 mRNAs, and recombinant DNA or RNA molecules that contain a 109P1D4 polynucleotide. A number of methods for amplifying and/or detecting the presence of 109P1 D4 polynucleotides are well known in the art and can be employed in the practice of this aspect of the invention.

In one embodiment, a method for detecting a 109P1 D4 mRNA in a biological sample comprises producing cDNA from the sample by reverse transcription using at least one primer ; amplifying the cDNA so produced using a 109P1 D4 polynucleotides as sense and antisense primers to amplify 109PI D4 cDNAs therein ; and detecting the presence of the amplified 109P1D4 cDNA. Optionally, the sequence of the amplified 109P1D4 cDNA can be determined.

In another embodiment, a method of detecting a 109P1 D4 gene in a biological sample comprises first isolating genomic DNA from the sample ; amplifying the isolated genomic DNA using 109P1 D4 polynucleotides as sense and antisense primers ; and detecting the presence of the amplified 109P1D4 gene. Any number of appropriate sense and antisense probe combinations can be designed from a 109P1 D4 nucleotide sequence (see, e. g., Figure 2) and used for this purpose.

The invention also provides assays for detecting the presence of a 109P1 D4 protein in a tissue or other biological sample such as serum, semen, bone, prostate, urine, cell preparations, and the like. Methods for detecting a 109P1 D4-related protein are also well known and include, for example, immunoprecipitation, immunohistochemical analysis, Western blot analysis, molecular binding assays, ELISA, ELIFA and the like. For example, a method of detecting the presence of a 109P1 D4-related protein in a biological sample comprises first contacting the sample with a 109P1 D4 antibody, a 109P1 D4-reactive fragment thereof, or a recombinant protein containing an antigen-binding region of a 109P1D4 antibody ; and then detecting the binding of 109P1D4-related protein in the sample.

Methods for identifying a cell that expresses 109P1 D4 are also within the scope of the invention. In one embodiment, an assayforidentfying acell thatexpressesa 109P1D4genecomprisesdetecting thepresenceof 109P1D4mRNAin the cell.

Methods for the detection of particular mRNAs in cells are well known and include, for example, hybridization assays using complementary DNA probes (such as in situ hybridization using labeled 109P1 D4 riboprobes, Northern blot and related techniques) and various nucleic acid amplification assays (such as RT-PCR using complementary primers specific for 109P1 D4, and other amplification type detection methods, such as, for example, branched DNA, SISBA, TMA and the like). Alternatively, an assay for identifying a cell that expresses a 109P1 D4 gene comprises detecting the presence of 109P1 D4-related protein in the cell or secreted by the cell. Various methods for the detection of proteins are well known in the art and are employed for the detection of 109P1 D4-related proteins and cells that express 109P1 D4-related proteins.

109P1 D4 expression analysis is also useful as a tool for identifying and evaluating agents that modulate 109P1 D4 gene expression. For example, 109P1 D4 expression is significantly upregulated in prostate cancer, and is expressed in cancers of the tissues listed in Table). identification of a molecule or biological agent that inhibits 109P1 D4 expression or over- expression in cancer cells is of therapeutic value. For example, such an agent can be identified by using a screen that quantifies 109P1 D4 expression by RT-PCR, nucleic acid hybridization or antibody binding.

VIII.) Methods for Monitoring the Status of 109P1D4related Genes and Their Products Oncogenesis is known to be a multistep process where cellular growth becomes progressively dysregulated and cells progress from a normal physiological state to precancerous and then cancerous states (see, e. g., Alers et al., Lab Invest. 77 (5) : 437-438 (1997) and Isaacs et al., Cancer Surv. 23 : 19-32 (1995)). In this context, examining a biological sample for evidence of dysregulated cell growth (such as aberrant 109P1 D4 expression in cancers) allows for early detection of such aberrant physiology, before a pathologic state such as cancer has progressed to a stage that therapeutic options are more limited and or the prognosis is worse. In such examinations, the status of 109P1 D4 in a biological sample of interest can be compared, for example, to the status of 109P1 D4 in a corresponding normal sample (e. g. a sample from that individual or alternatively another individual that is not affected by a pathology). An alteration in the status of 109P1 D4 in the biological sample (as compared to the normal sample) provides evidence of dysregulated cellular growth. In addition to using a biological sample that is not affected by a pathology as a normal sample, one can also use a predetermined normative value such as a predetermined normal level of mRNA expression (see, e. g., Grever et a/., J. Comp. Neurol. 1996 Dec 9 ; 376 (2) : 306-14 and U. S. Patent No. 5, 837, 501) to compare 109P1D4 status in a sample.

The term"status"in this context is used according to its art accepted meaning and refers to the condition or state of a gene and its products. Typically, skilled artisans use a number of parameters to evaluate the condition or state of a gene and its products. These include, but are not limited to the location of expressed gene products (including the location of 109P1 D4 expressing cells) as well as the level, and biological activity of expressed gene products (such as 109P1 D4 mRNA, polynucleotides and polypeptides). Typically, an alteration in the status of 109P1 D4 comprises a change in the location of 109P1 D4 and/or 109P1 D4 expressing cells and/or an increase in 109P1 D4 mRNA and/or protein expression.

109P1 D4 status in a sample can be analyzed by a number of means well known in the art, including without limitation, immunohistochemical analysis, in situ hybridization, RT-PCR analysis on laser capture micro-dissected samples, Western blot analysis, and tissue array analysis. Typical protocols for evaluating the status of a 109P1 D4 gene and gene products are found, for example in Ausubel et al. eds., 1995, Current Protocols In Molecular Biology, Units 2 (Northern Blotting), 4 (Southern Blotting), 15 (Immunoblotting) and 18 (PCR Analysis). Thus, the status of 109P1 D4 in a biological sample is evaluated by various methods utilized by skilled artisans including, but not limited to genomic Southern analysis (to examine, for example perturbations in a 109P1D4 gene), Northern analysis and/or PCR analysis of 109P1D4 mRNA (to examine, for example alterations in the polynucleotide sequences or expression levels of 109P1D4 mRNAs), and, Western and/or immunohistochemical analysis (to examine, for example alterations in polypeptide sequences, alterations in polypeptide localization within a sample, alterations in expression levels of 109P1 D4 proteins and/or associations of 109P1D4 proteins with polypeptide binding partners). Detectable 109P1D4 polynucleotides include, for example, a 109P1D4 gene fragment thereof, 109P1 D4 mRNA, alternative splice variants, 109P1 D4 mRNAs, and recombinant DNA or RNA molecules containing a 1 O9P1 D4 polynucleotide The expression profile of 109P1 D4 makes it a diagnostic marker for local and/or metastasized disease, and provides information on the growth or oncogenic potential of a biological sample. in particular, the status of 109P1 D4 provides information useful for predicting susceptibility to particular disease stages, progression, and/or tumor aggressiveness. The invention provides methods and assays for determining 109P1 D4 status and diagnosing cancers that express 109P1 D4, such as cancers of the tissues listed in Table I. For example, because 109P1 D4 mRNA is so highly expressed in prostate and other cancers relative to normal prostate tissue, assays that evaluate the levels of 109P1D4 mRNA transcripts or proteins in a biological sample can be used to diagnose a disease associated with 109P1 D4 dysregulation, and can provide prognostic information useful in defining appropriate therapeutic options.

The expression status of 109P1D4 provides information including the presence, stage and location of dysplastic, precancerous and cancerous cells, predicting susceptibility to various stages of disease, and/or for gauging tumor aggressiveness. Moreover, the expression profile makes it useful as an imaging reagent for metastasized disease.

Consequently, an aspect of the invention is directed to the various molecular prognostic and diagnostic methods for examining the status of 109P1 D4 in biological samples such as those from individuals suffering from, or suspected of suffering from a pathology characterized by dysregulated cellular growth, such as cancer.

As described above, the status of 109P1 D4 in a biological sample can be examined by a number of well-known procedures in the art. For example, the status of 109P1D4 in a biological sample taken from a specific location in the body can be examined by evaluating the sample for the presence or absence of 109P1 D4 expressing cells (e. g. those that express 109P1 D4 mRNAs or proteins). This examination can provide evidence of dysregulated cellular growth, for example, when 109P1D4-expressing cells are found in a biological sample that does not normally contain such cells (such as a lymph node), because such alterations in the status of 109P1D4 in a biological sample are often associated with dysregulated cellular growth. Specifically, one indicator of dysregulated cellular growth is the metastases of cancer cells from an organ of origin (such as the prostate) to a different area of the body (such as a lymph node). In this context, evidence of dysregulated cellular growth is important for example because occult lymph node metastases can be detected in a substantial proportion of patients with prostate cancer, and such metastases are associated with known predictors of disease progression (see, e. g., Murphy et al., Prostate 42 (4) : 315-317 (2000) ; Su et al., Semin. Surg. Oncol. 18 (1) : 17-28 (2000) and Freeman et al., J Urol 1995 Aug 154 (2 Pt 1) : 474-8).

In one aspect, the invention provides methods for monitoring 109P1 D4 gene products by determining the status of 109P1D4 gene products expressed by cells from an individual suspected of having a disease associated with dysregulated cell growth (such as hyperplasia or cancer) and then comparing the status so determined to the status of 109P1D4 gene products in a corresponding normal sample. The presence of aberrant 109P1 D4 gene products in the test sample relative to the normal sample provides an indication of the presence of dysregulated cell growth within the cells of the individual.

In another aspect, the invention provides assays useful in determining the presence of cancer in an individual, comprising detecting a significant increase in 109P1D4 mRNA or protein expression in a test cell or tissue sample relative to expression levels in the corresponding normal cell or tissue. The presence of 109P1D4 mRNA can, for example, be evaluated in tissues including but not limited to those listed in Table !. The presence of significant 109P1D4 expression in any of these tissues is useful to indicate the emergence, presence and/or severity of a cancer, since the corresponding normal tissues do not express 109P1 D4 mRNA or express it at lower levels.

In a related embodiment, 109P1 D4 status is determined at the protein level rather than at the nucleic acid level. For example, such a method comprises determining the level of 109P1 D4 protein expressed by cells in a test tissue sample and comparing the level so determined to the level of 109P1 D4 expressed in a corresponding normal sample. In one embodiment, the presence of 109P1 D4 protein is evaluated, for example, using immunohistochemical methods. 109P1 D4 antibodies or binding partners capable of detecting 109P1 D4 protein expression are used in a variety of assay formats well known in the art for this purpose.

In a further embodiment, one can evaluate the status of 109P1 D4 nucleotide and amino acid sequences in a biological sample in order to identify perturbations in the structure of these molecules. These perturbations can include insertions, deletions, substitutions and the like. Such evaluations are useful because perturbations in the nucleotide and amino acid sequences are observed in a large number of proteins associated with a growth dysregulated phenotype (see, e. g., Marrogi et al., 1999, J.

Cutan. Pathol. 26 (8) : 369-378). For example, a mutation in the sequence of 109P1 D4 may be indicative of the presence or promotion of a tumor. Such assays therefore have diagnostic and predictive value where a mutation in 109P1 D4 indicates a potential loss of function or increase in tumor growth.

A wide variety of assays for observing perturbations in nucleotide and amino acid sequences are well known in the art.

For example, the size and structure of nucleic acid or amino acid sequences of 109P1 D4 gene products are observed by the Northern, Southern, Western, PCR and DNA sequencing protocols discussed herein. In addition, other methods for observing perturbations in nucleotide and amino acid sequences such as single strand conformation polymorphism analysis are well known in the art (see, e. g., U. S. Patent Nos. 5, 382, 510 issued 7 September 1999, and 5, 952, 170 issued 17 January 1995).

Additionally, one can examine the methylation status of a 109P1D4 gene in a biological sample. Aberrant demethylation and/or hypermethylation of CpG islands in gene 5'regulatory regions frequently occurs in immortalized and transformed cells, and can result in altered expression of various genes. For example, promoter hypermethylation of the pi-class glutathione S-transferase (a protein expressed in normal prostate but not expressed in >90% of prostate carcinomas) appears to permanently silence transcription of this gene and is the most frequently detected genomic alteration in prostate carcinomas (De Marzo et al., Am. J. Pathol. 155 (6) : 1985-1992 (1999)). In addition, this alteration is present in at least 70% of cases of high-grade prostatic intraepithelial neoplasia (PIN) (Brooks et al., Cancer Epidemiol. Biomarkers Prev., 1998, 7 : 531-536). In another example, expression of the LAGE-l tumor specific gene (which is not expressed in normal prostate but is expressed in 25-50% of prostate cancers) is induced by deoxy-azacytidine in lymphoblastoid cells, suggesting that tumoral expression is due to demethylation (Lethe et al., Int. J. Cancer 76 (6) : 903-908 (1998)). A variety of assays for examining methylation status of a gene are well known in the art. For example, one can utilize, in Southern hybridization approaches, methylation-sensitive restriction enzymes that cannot cleave sequences that contain methylated CpG sites to assess the methylation status of CpG islands. In addition, MSP (methylation specific PCR) can rapidly profile the methylation status of all the CpG sites present in a CpG island of a given gene. This procedure involves initial modification of DNA by sodium bisulfite (which will convert all unmethylated cytosines to uracil) followed by amplification using primers specific for methylated versus unmethylated DNA. Protocols involving methylation interference can also be found for example in Current Protocols In Molecular Biology, Unit 12, Frederick M. Ausubel et al. eds., 1995.

Gene amplification is an additional method for assessing the status of 109P1 D4. Gene amplification is measured in a sample directly, for example, by conventional Southern blotting or Northern blotting to quantitate the transcription of mRNA (Thomas, 1980, Proc. Natl. Acad. Sci. USA, 77 : 5201-5205), dot blotting (DNA analysis), or in situ hybridization, using an appropriately labeled probe, based on the sequences provided herein. Alternatively, antibodies are employed that recognize specific duplexes, including DNA duplexes, RNA duplexes, and DNA-RNA hybrid duplexes or DNA-protein duplexes. The antibodies in turn are labeled and the assay carried out where the duplex is bound to a surface, so that upon the formation of duplex on the surface, the presence of antibody bound to the duplex can be detected.

Biopsied tissue or peripheral blood can be conveniently assayed for the presence of cancer cells using for example, Northern, dot blot or RT-PCR analysis to detect 109P1 D4 expression. The presence of RT-PCR amplifiable 109P1 D4 mRNA provides an indication of the presence of cancer. RT-PCR assays are well known in the art. RT-PCR detection assays for tumor cells in peripheral blood are currently being evaluated for use in the diagnosis and management of a number of human solid tumors. In the prostate cancer field, these include RT-PCR assays for the detection of cells expressing PSA and PSM (Verkaik et al., 1997, Urol. Res. 25 : 373-384 ; Ghossein era/., 1995, J. Clin. Oncol. 13 : 1195-2000 ; Heston et al., 1995, Clin. Chem. 41 : 1687- 1688).

A further aspect of the invention is an assessment of the susceptibility that an individual has for developing cancer. In one embodiment, a method for predicting susceptibility to cancer comprises detecting 109P1 D4 mRNA or 109P1 D4 protein in a tissue sample, its presence indicating susceptibility to cancer, wherein the degree of 109P1 D4 mRNA expression correlates to the degree of susceptibility. In a specific embodiment, the presence of 109P1 D4 in prostate or other tissue is examined, with the presence of 109P1 D4 in the sample providing an indication of prostate cancer susceptibility (or the emergence or existence of a prostate tumor). Similarly, one can evaluate the integrity 109P1 D4 nucleotide and amino acid sequences in a biological sample, in order to identify perturbations in the structure of these molecules such as insertions, deletions, substitutions and the like. The presence of one or more perturbations in 109P1 D4 gene products in the sample is an indication of cancer susceptibility (or the emergence or existence of a tumor).

The invention also comprises methods for gauging tumor aggressiveness. In one embodiment, a method for gauging aggressiveness of a tumor comprises determining the level of 109P1 D4 mRNA or 109P1 D4 protein expressed by tumor cells, comparing the level so determined to the level of 109P1 D4 mRNA or 109P1 D4 protein expressed in a corresponding normal tissue taken from the same individual or a normal tissue reference sample, wherein the degree of 109P1 D4 mRNA or 109P1D4 protein expression in the tumor sample relative to the normal sample indicates the degree of aggressiveness. In a specific embodiment, aggressiveness of a tumor is evaluated by determining the extent to which 109P1 D4 is expressed in the tumor cells, with higher expression levels indicating more aggressive tumors. Another embodiment is the evaluation of the integrity of 109P1D4 nucleotide and amino acid sequences in a biological sample, in order to identify perturbations in the structure of these molecules such as insertions, deletions, substitutions and the like. The presence of one or more perturbations indicates more aggressive tumors.

Another embodiment of the invention is directed to methods for observing the progression of a malignancy in an individual over time. In one embodiment, methods for observing the progression of a malignancy in an individual over time comprise determining the level of 109P1D4 mRNA or 109P1D4 protein expressed by cells in a sample of the tumor, comparing the level so determined to the level of 109P1 D4 mRNA or 109P1 D4 protein expressed in an equivalent tissue sample taken from the same individual at a different time, wherein the degree of 109P1 D4 mRNA or 109P1 D4 protein expression in the tumor sample over time provides information on the progression of the cancer. In a specific embodiment, the progression of a cancer is evaluated by determining 109P1 D4 expression in the tumor cells over time, where increased expression over time indicates a progression of the cancer. Also, one can evaluate the integrity 109P1 D4 nucleotide and amino acid sequences in a biological sample in order to identify perturbations in the structure of these molecules such as insertions, deletions, substitutions and the like, where the presence of one or more perturbations indicates a progression of the cancer.

The above diagnostic approaches can be combined with any one of a wide variety of prognostic and diagnostic protocols known in the art. For example, another embodiment of the invention is directed to methods for observing a coincidence between the expression of 109P1 D4 gene and 109P1 D4 gene products (or perturbations in 109P1 D4 gene and 109P1 D4 gene products) and a factor that is associated with malignancy, as a means for diagnosing and prognosticating the status of a tissue sample. A wide variety of factors associated with malignancy can be utilized, such as the expression of genes associated with malignancy (e. g. PSA, PSCA and PSM expression for prostate cancer etc.) as well as gross cytological observations (see, e. g., Bocking etal., 1984, Anal. Quant. Cytol. 6 (2) : 74-88 ; Epstein, 1995, Hum. Pathol. 26 (2) : 223-9 ; Thorson et al., 1998, Mod.

Pathol. 11 (6) : 543-51 ; Baisden et al., 1999, Am. J. Surg. Pathol. 23 (8) : 918-24). Methods for observing a coincidence between the expression of 109P1D4 gene and 109P1D4 gene products (or perturbations in 109P1D4 gene and 109PI D4 gene products) and another factor that is associated with malignancy are useful, for example, because the presence of a set of specific factors that coincide with disease provides information crucial for diagnosing and prognosticating the status of a tissue sample.

In one embodiment, methods for observing a coincidence between the expression of 109P1 D4 gene and 109P1 D4 gene products (or perturbations in 109P1 D4 gene and 109P1 D4 gene products) and another factor associated with malignancy entails detecting the overexpression of 109P1D4 mRNA or protein in a tissue sample, detecting the overexpression of PSA mRNA or protein in a tissue sample (or PSCA or PSM expression), and observing a coincidence of 109P1 D4 mRNA or protein and PSA mRNA or protein overexpression (or PSCA or PSM expression). In a specific embodiment, the expression of 109P1 D4 and PSA mRNA in prostate tissue is examined, where the coincidence of 109P1D4 and PSA mRNA overexpression in the sample indicates the existence of prostate cancer, prostate cancer susceptibility or the emergence or status of a prostate tumor.

Methods for detecting and quantifying the expression of 109P1 D4 mRNA or protein are described herein, and standard nucleic acid and protein detection and quantification technologies are well known in the art. Standard methods for the detection and quantification of 109P1 D4 mRNA include in situ hybridization using labeled 109P1 D4 riboprobes, Northern blot and related techniques using 109P1 D4 polynucleotide probes, RT-PCR analysis using primers specific for 109P1D4, and other amplification type detection methods, such as, for example, branched DNA, SISBA, TMA and the like. In a specific embodiment, semi- quantitative RT-PCR is used to detect and quantify 109P1 D4 mRNA expression. Any number of primers capable of amplifying 109P1 D4 can be used for this purpose, including but not limited to the various primer sets specifically described herein. In a specific embodiment, polyclonal or monoclonal antibodies specifically reactive with the wild-type 109P1 D4 protein can be used in an immunohistochemical assay of biopsied tissue.

IX.) Identification of Molecules That Interact With 109P1 D4 The 109P1D4 protein and nucleic acid sequences disclosed herein allow a skilled artisan to identify proteins, small molecules and other agents that interact with 109P1 D4, as well as pathways activated by 109P1 D4 via any one of a variety of art accepted protocols. For example, one can utilize one of the so-called interaction trap systems (also referred to as the "two-hybrid assay"). In such systems, molecules interact and reconstitute a transcription factor which directs expression of a reporter gene, whereupon the expression of the reporter gene is assayed. Other systems identify protein-protein interactions in vivo through reconstitution of a eukaryotic transcriptional activator, see, e. g., U. S. Patent Nos. 5, 955, 280 issued 21 September 1999, 5, 925, 523 issued 20 July 1999, 5, 846, 722 issued 8 December 1998 and 6, 004, 746 issued 21 December 1999. Algorithms are also available in the art for genome-based predictions of protein function (see, e. g., Marcotte, et al., Nature 402 : 4 November 1999, 83-86).

Alternatively one can screen peptide libraries to identify molecules that interact with 109P1 D4 protein sequences.

In such methods, peptides that bind to 109P1D4 are identified by screening libraries that encode a random or controlled collection of amino acids. Peptides encoded by the libraries are expressed as fusion proteins of bacteriophage coat proteins, the bacteriophage particles are then screened against the 109P1D4 protein (s).

Accordingly, peptides having a wide variety of uses, such as therapeutic, prognostic or diagnostic reagents, are thus identified without any prior information on the structure of the expected ligand or receptor molecule. Typical peptide libraries and screening methods that can be used to identify molecules that interact with 109P1 D4 protein sequences are disclosed for example in U. S. Patent Nos. 5, 723, 286 issued 3 March 1998 and 5, 733, 731 issued 31 March 1998.

Alternatively, cell lines that express 109P1D4 are used to identify protein-protein interactions mediated by 109P1D4. Such interactions can be examined using immunoprecipitation techniques (see, e. g., Hamilton B. J., et al Biochem. Biophys. Res. Commun. 1999, 261 : 646-51). 109P1D4 protein can be immunoprecipitated from 109P1D4- expressing cell lines using anti-109P1 D4 antibodies. Alternatively, antibodies against His-tag can be used in a cell line engineered to express fusions of 109P1D4 and a His-tag (vectors mentioned above). The immunoprecipitated complex can be examined for protein association by procedures such as Western blotting, 35S-methionine labeling of proteins, protein microsequencing, silver staining and two-dimensional gel electrophoresis.

Small molecules and ligands that interact with 109P1D4 can be identified through related embodiments of such screening assays. For example, small molecules can be identified that interfere with protein function, including molecules that interfere with 109P1 D4's ability to mediate phosphorylation and de-phosphorylation, interaction with DNA or RNA molecules as an indication of regulation of cell cycles, second messenger signaling or tumorigenesis. Similarly, small molecules that modulate 109P1 D4-related ion channel, protein pump, or cell communication functions are identified and used to treat patients that have a cancer that expresses 109P1 D4 (see, e. g., Hille, B., ionic Channels of Excitable Membranes 2nd Ed., Sinauer Assoc., Sunderland, MA, 1992). Moreover, ligands that regulate 109P1 D4 function can be identified based on their ability to bind 109P1D4 and activate a reporter construct. Typical methods are discussed for example in U. S. Patent No. 5, 928, 868 issued 27 July 1999, and include methods for forming hybrid ligands in which at least one ligand is a small molecule. In an illustrative embodiment, cells engineered to express a fusion protein of 109P1D4 and a DNA-binding protein are used to co-express a fusion protein of a hybrid ligand/small molecule and a cDNA library transcriptional activator protein. The cells further contain a reporter gene, the expression of which is conditioned on the proximity of the first and second fusion proteins to each other, an event that occurs only if the hybrid ligand binds to target sites on both hybrid proteins. Those cells that express the reporter gene are selected and the unknown small molecule or the unknown ligand is identified. This method provides a means of identifying modulators, which activate or inhibit 109PI D4.

An embodiment of this invention comprises a method of screening for a molecule that interacts with a 109P1 D4 amino acid sequence shown in Figure 2 or Figure 3, comprising the steps of contacting a population of molecules with a 109P1D4 amino acid sequence, allowing the population of molecules and the 109P1D4 amino acid sequence to interact under conditions that facilitate an interaction, determining the presence of a molecule that interacts with the 109P1 D4 amino acid sequence, and then separating molecules that do not interact with the 109P1D4 amino acid sequence from molecules that do. In a specific embodiment, the method further comprises purifying, characterizing and identifying a molecule that interacts with the 109P1D4 amino acid sequence. The identified molecule can be used to modulate a function performed by 109P1 D4. In a preferred embodiment, the 109P1 D4 amino acid sequence is contacted with a library of peptides.

NJ Therapeutic Methods and Compositions The identification of 109P1 D4 as a protein that is normally expressed in a restricted set of tissues, but which is also expressed in cancers such as those listed in Table I, opens a number of therapeutic approaches to the treatment of such cancers.

Of note, targeted antitumor therapies have been useful even when the targeted protein is expressed on normal tissues, even vital normal organ tissues. A vital organ is one that is necessary to sustain life, such as the heart or colon. A non-vital organ is one that can be removed whereupon the individual is still able to survive. Examples of non-vital organs are ovary, breast, and prostate.

For example, Herceptin0 is an FDA approved pharmaceutical that has as its active ingredient an antibody which is immunoreactive with the protein variously known as HER2, HER2/neu, and erb-b-2. It is marketed by Genentech and has been a commercially successful antitumor agent. Herceptin sales reached almost $400 million in 2002. Herceptin is a treatment for HER2 positive metastatic breast cancer. However, the expression of HER2 is not limited to such tumors. The same protein is expressed in a number of normal tissues. In particular, it is known that HER2/neu is present in normal kidney and heart, thus these tissues are present in all human recipients of Herceptin. The presence of HER2/neu in normal kidney is also confirmed by Latif, Z., et al., B. J. U. Intemational (2002) 89 : 5-9. As shown in this article (which evaluated whether renal cell carcinoma should be a preferred indication for anti-HER2 antibodies such as Herceptin) both protein and mRNA are produced in benign renal tissues. Notably, HER2/neu protein was strongly overexpressed in benign renal tissue.

Despite the fact that HER2/neu is expressed in such vital tissues as heart and kidney, Herceptin is a very useful, FDA approved, and commercially successful drug. The effect of Herceptin on cardiac tissue, i. e.,"cardiotoxicity,"has merely been a side effect to treatment. When patients were treated with Herceptin alone, significant cardiotoxicity occurred in a very low percentage of patients.

Of particular note, although kidney tissue is indicated to exhibit normal expression, possibly even higher expression than cardiac tissue, kidney has no appreciable Herceptin side effect whatsoever. Moreover, of the diverse array of normal tissues in which HER2 is expressed, there is very little occurrence of any side effect. Only cardiac tissue has manifested any appreciable side effect at all. A tissue such as kidney, where HER2/neu expression is especially notable, has not been the basis for any side effect.

Furthermore, favorable therapeutic effects have been found for antitumor therapies that target epidermal growth factor receptor (EGFR). EGFR is also expressed in numerous normal tissues. There have been very limited side effects in normal tissues following use of anti-EGFR therapeutics.

Thus, expression of a target protein in normal tissue, even vital normal tissue, does not defeat the utility of a targeting agent for the protein as a therapeutic for certain tumors in which the protein is also overexpressed.

Accordingly, therapeutic approaches that inhibit the activity of a 109P1 D4 protein are useful for patients suffering from a cancer that expresses 109P1D4. These therapeutic approaches generally fall into two classes. One class comprises various methods for inhibiting the binding or association of a 109P1 D4 protein with its binding partner or with other proteins.

Another class comprises a variety of methods for inhibiting the transcription of a 109P1D4 gene or translation of 109P1D4 mRNA.

X. A.) Anti-Cancer Vaccines The invention provides cancer vaccines comprising a 109P1 D4-related protein or 109P1 D4-related nucleic acid. In view of the expression of 109P1 D4, cancer vaccines prevent and/or treat 109P1 D4-expressing cancers with minimal or no effects on non-target tissues. The use of a tumor antigen in a vaccine that generates humoral and/or cell-mediated immune responses as anti-cancer therapy is well known in the art and has been employed in prostate cancer using human PSMA and rodent PAP immunogens (Hodge et al., 1995, Int. J. Cancer 63 : 231-237 ; Fong et al., 1997, J. Immunol. 159 : 3113-3117).

Such methods can be readily practiced by employing a 109P1D4-retated protein, or a 109P1D4-encoding nucleic acid molecule and recombinant vectors capable of expressing and presenting the 109P1 D4 immunogen (which typically comprises a number of antibody or T cell epitopes). Skilled artisans understand that a wide variety of vaccine systems for delivery of immunoreactive epitopes are known in the art (see, e. g., Heryln et al., Ann Med 1999 Feb 31 (1) : 66-78 ; Maruyama et al., Cancer immune) lmmunother 2000 Jun 49 (3) : 123-32) Briefly, such methods of generating an immune response (e. g. humoral and/or cell-mediated) in a mammal, comprise the steps of : exposing the mammal's immune system to an immunoreactive epitope (e. g. an epitope present in a 109P1 D4 protein shown in Figure 3 or analog or homolog thereof) so that the mammal generates an immune response that is specific for that epitope (e. g. generates antibodies that specifically recognize that epitope). In a preferred method, a 109P1 D4 immunogen contains a biological motif, see e. g., Tables VIII-XXI and XXII-XLIX, or a peptide of a size range from 109P1 D4 indicated in Figure 5, Figure 6, Figure 7, Figure 8, and Figure 9.

The entire 109P1 D4 protein, immunogenic regions or epitopes thereof can be combined and delivered by various means. Such vaccine compositions can include, for example, lipopeptides (e. g., Vitiello, A. et a/., J. Clin. Invest. 95 : 341, 1995), peptide compositions encapsulated in poly (DL-lactide-co-glycolide) ("PLG") microspheres (see, e. g., Eldridge, et al., Molec. Immunol. 28 : 287-294, 1991 : Alonso et al., Vaccine 12 : 299-306, 1994 ; Jones et al., Vaccine 13 : 675-681, 1995), peptide compositions contained in immune stimulating complexes (ISCOMS) (see, e. g., Takahashi ef al., Nature 344 : 873- 875, 1990 ; Hu et al., Clin Exp Immunol. 113 : 235-243, 1998), multiple antigen peptide systems (MAPs) (see e. g., Tam, J. P., Proc. Natl. Acad. Sci. U. S. A. 85 : 5409-5413, 1988 ; Tam, J. P., J. Immunol. Methods 196 : 17-32, 1996), peptides formulated as multivalent peptides ; peptides for use in ballistic delivery systems, typically crystallized peptides, viral delivery vectors (Perkus, M. E. et al., In : Concepts in vaccine development, Kaufmann, S. H. E., ed., p. 379, 1996 ; Chakrabarti, S. et al., Nature 320 : 535, 1986 ; Hu, S. L. et al., Nature 320 : 537, 1986 ; Kieny, M.-P. et al., AIDS BiolTechnology 4 : 790, 1986 ; Top, F.

H. et al., J. Infect. Dis. 124 : 148, 1971 ; Chanda, P. K. et al., Virology 175 : 535, 1990), particles of viral or synthetic origin (e. g., Kofler, N. et al., J. ImmunoL Methods. 192 : 25, 1996 ; Eldridge, J. H. et al., Sem. Hematol. 30 : 16, 1993 ; Falo, L. D., Jr. et al., Nature Med. 7 : 649, 1995), adjuvants (Warren, H. S., Vogel, F. R., and Chedid, L. A. Annu. Rev. Immunol. 4 : 369, 1986 ; Gupta, R. K. et al., Vaccine 11 : 293, 1993), liposomes (Reddy, R. etaL, J. ImmunoL 148 : 1585, 1992 ; Rock, K. L., ImmunoL Today 17 : 131, 1996), or, naked or particle absorbed cDNA (Ulmer, J. B. et al., Science 259 : 1745, 1993 ; Robinson, H. L., Hunt, L. A., and Webster, R. G., Vaccine 11 : 957, 1993 ; Shiver, J. W. et aL, In : Concepts in vaccine development, Kaufmann, S. H. E., ed., p. 423, 1996 ; Cease, K. B., and Berzofsky, J. A., Annu. Rev. Immunol. 12 : 923, 1994 and Eldridge, J. H. et al., Sem. HematoL 30 : 16, 1993). Toxin-targeted delivery technologies, also known as receptor mediated targeting, such as those of Avant Immunotherapeutics, Inc. (Needham, Massachusetts) may also be used. in patients with 109P1 D4-associated cancer, the vaccine compositions of the invention can also be used in conjunction with other treatments used for cancer, e. g., surgery, chemotherapy, drug therapies, radiation therapies, etc. including use in combination with immune adjuvants such as IL-2, IL-12, GM-CSF, and the like.

Cellular Vaccines : CTL epitopes can be determined using specific algorithms to identify peptides within 109P1 D4 protein that bind corresponding HLA alleles (see e. g., Table IV ; Eimer and Epimatri) (Fm, Brown University (URL brown. edu/Research/TB- HIV Lab/epimatrix/epimatrix. html) ; and, BIMAS, (URL bimas. dcrt. nih. gov/; SYFPEITHI at URL syfpeithi. bmi-heidelberg. com/).

In a preferred embodiment, a 109P1 D4 immunogen contains one or more amino acid sequences identified using techniques well known in the art, such as the sequences shown in Tables VIII-XXI and XXII-XLIX or a peptide of 8, 9, 10 or 11 amino acids specified by an HLA Class I motif/supermotif (e. g., Table IV (A), Table IV (D), or Table IV (E)) and/or a peptide of at least 9 amino acids that comprises an HLA Class II motif/supermotif (e. g., Table IV (B) or Table IV (C)). As is appreciated in the art, the HLA Class I binding groove is essentially closed ended so that peptides of only a particular size range can fit into the groove and be bound, generally HLA Class I epitopes are 8, 9, 10, or 11 amino acids long. In contrast, the HLA Class II binding groove is essentially open ended ; therefore a peptide of about 9 or more amino acids can be bound by an HLA Class II molecule. Due to the binding groove differences between HLA Class I and II, HLA Class I motifs are length specific, i. e., position two of a Class l motif is the second amino acid in an amino to carboxyl direction of the peptide. The amino acid positions in a Class II motif are relative only to each other, not the overall peptide, i. e., additional amino acids can be attached to the amino and/or carboxyl termini of a motif-bearing sequence. HLA Class II epitopes are often 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 amino acids long, or longer than 25 amino acids.

Antibody-based Vaccines A wide variety of methods for generating an immune response in a mammal are known in the art (for example as the first step in the generation of hybridomas). Methods of generating an immune response in a mammal comprise exposing the mammal's immune system to an immunogenic epitope on a protein (e. g. a 109P1D4 protein) so that an immune response is generated. A typical embodiment consists of a method for generating an immune response to 109P1D4 in a host, by contacting the host with a sufficient amount of at least one 109P1 D4 B cell or cytotoxic T-cell epitope or analog thereof ; and at least one periodic interval thereafter re-contacting the host with the 109P1 D4 B cell or cytotoxic T-cell epitope or analog thereof. A specific embodiment consists of a method of generating an immune response against a 109P1 D4- related protein or a man-made multiepitopic peptide comprising : administering 109P1D4 immunogen (e. g. a 109P1D4 protein or a peptide fragment thereof, a 109P1D4 fusion protein or analog etc.) in a vaccine preparation to a human or another mammal. Typically, such vaccine preparations further contain a suitable adjuvant (see, e. g., U. S. Patent No.

6, 146, 635) or a universal helper epitope such as a PADRETM peptide (Epimmune Inc., San Diego, CA ; see, e. g., Alexander et al., J. Immunol. 2000 164 (3) ; 164 (3) : 1625-1633 ; Alexander et al., immunity 19941 (9) : 751-761 and Alexander et al., Immunol. Res. 199818 (2) : 79-92). An alternative method comprises generating an immune response in an individual against a 109P1D4 immunogen by : administering in vivo to muscle or skin of the individual's body a DNA molecule that comprises a DNA sequence that encodes a 109P1D4 immunogen, the DNA sequence operatively linked to regulatory sequences which control the expression of the DNA sequence ; wherein the DNA molecule is taken up by cells, the DNA sequence is expressed in the cells and an immune response is generated against the immunogen (see, e. g., U. S. Patent No.

5, 962, 428). Optionally a genetic vaccine facilitator such as anionic lipids ; saponins ; lectins ; estrogenic compounds ; hydroxylated lower alkyls ; dimethyl sulfoxide ; and urea is also administered. In addition, an antiidiotypic antibody can be administered that mimics 109P1D4, in order to generate a response to the target antigen.

Nucleic Acid Vaccines : Vaccine compositions of the invention include nucleic acid-mediated modalities. DNA or RNA that encode protein (s) of the invention can be administered to a patient. Genetic immunization methods can be employed to generate prophylactic or therapeutic humoral and cellular immune responses directed against cancer cells expressing 109PI D4.

Constructs comprising DNA encoding a 109P1 D4-related protein/immunogen and appropriate regulatory sequences can be injected directly into muscle or skin of an individual, such that the cells of the muscle or skin take-up the construct and express the encoded 109PI D4 protein/immunogen. Alternatively, a vaccine comprises a 109P1 D4-related protein.

Expression of the 109P1 D4-related protein immunogen results in the generation of prophylactic or therapeutic humoral and cellular immunity against cells that bear a 109P1D4 protein. Various prophylactic and therapeutic genetic immunization techniques known in the art can be used (for review, see information and references published at Internet address genweb. com). Nucleic acid-based delivery is described, for instance, in Wolff et. a/., Science 247 : 1465 (1990) as well as U. S. Patent Nos. 5, 580, 859 ; 5, 589, 466 ; 5, 804, 566 ; 5, 739, 118 ; 5, 736, 524 ; 5, 679, 647 ; WO 98/04720. Examples of DNA- based delivery technologies include"naked DNA", facilitated (bupivicaine, polymers, peptide-mediated) delivery, cationic lipid complexes, and particle-mediated ("gene gun") or pressure-mediated delivery (see, e. g., U. S. Patent No. 5, 922, 687).

For therapeutic or prophylactic immunization purposes, proteins of the invention can be expressed via viral or bacterial vectors. Various viral gene delivery systems that can be used in the practice of the invention include, but are not limited to, vaccinia, fowipox, canarypox, adenovirus, influenza, poliovirus, adeno-associated virus, lentivirus, and sindbis virus (see, e. g., Restifo, 1996, Curr. Opin. Immunol. 8 : 658-663 ; Tsang et al. J. Natl. Cancer lnst. 87 : 982-990 (1995)). Non-viral delivery systems can also be employed by introducing naked DNA encoding a 109P1D4-related protein into the patient (e. g., intramuscularly or intradermally) to induce an anti-tumor response.

Vaccina virus is used, for example, as a vector to express nucleotide sequences that encode the peptides of the invention. Upon introduction into a host, the recombinant vaccinia virus expresses the protein immunogenic peptide, and thereby elicits a host immune response. Vaccinia vectors and methods useful in immunization protocols are described in, e. g., U. S. Patent No. 4, 722, 848. Another vector is BCG (Bacille Calmette Guerin). BCG vectors are described in Stover et al., Nature 351 : 456-460 (1991). A wide variety of other vectors useful for therapeutic administration or immunization of the peptides of the invention, e. g. adeno and adeno-associated virus vectors, retroviral vectors, Salmonella typhi vectors, detoxified anthrax toxin vectors, and the like, will be apparent to those skilled in the art from the description herein.

Thus, gene delivery systems are used to deliver a 109P1D4-related nucleic acid molecule. In one embodiment, the full- length human 109P1 D4 cDNA is employed. In another embodiment, 109P1 D4 nucleic acid molecules encoding specific cytotoxic T lymphocyte (CTL) and/or antibody epitopes are employed.

Ex Vivo Vaccines Various ex vivo strategies can also be employed to generate an immune response. One approach involves the use of antigen presenting cells (APCs) such as dendritic cells (DC) to present 109P1 D4 antigen to a patient's immune system. Dendritic cells express MHC class I and II molecules, B7 co-stimulator, and IL-12, and are thus highly specialized antigen presenting cells.

In prostate cancer, autologous dendritic cells pulsed with peptides of the prostate-specific membrane antigen (PSMA) are being used in a Phase I clinical trial to stimulate prostate cancer patients'immune systems (Tjoa et al., 1996, Prostate 28 : 65- 69 ; Murphy et al., 1996, Prostate 29 : 371-380). Thus, dendritic cells can be used to present 109P1D4 peptides to T cells in the context of MHC class f or 11 molecules. In one embodiment, autologous dendritic cells are pulsed with 109P1 D4 peptides capable of binding to MHC class I and/or class li molecules. In another embodiment, dendritic cells are pulsed with the complete 109P1D4 protein. Yet another embodiment involves engineering the overexpression of a 109P1D4 gene in dendritic cells using various implementing vectors known in the art, such as adenovirus (Arthur et al., 1997, Cancer Gene Ther. 4 : 17-25), retrovirus (Henderson et al., 1996, Cancer Res. 56 : 3763-3770), lentivirus, adeno-associated virus, DNA transfection (Ribas et al., 1997, Cancer Res. 57 : 2865-2869), or tumor-derived RNA transfection (Ashley et al., 1997, J. Exp.

Med. 186 : 1177-1182). Cells that express 109P1D4 can also be engineered to express immune modulators, such as GM- CSF, and used as immunizing agents.

X. B.) 109P1 D4 as a Target for Antibody-based Therapy 109P1 D4 is an attractive target for antibody-based therapeutic strategies. A number of antibody strategies are known in the art for targeting both extracellular and intracellular molecules (see, e. g., complement and ADCC mediated killing as well as the use of intrabodies). Because 109P1D4 is expressed by cancer cells of various lineages relative to corresponding normal cells, systemic administration of 109P1 D4-immunoreactive compositions are prepared that exhibit excellent sensitivity without toxic, non-specific and/or non-target effects caused by binding of the immunoreactive composition to non-target organs and tissues. Antibodies specifically reactive with domains of 109P1D4 are useful to treat 109P1 D4-expressing cancers systemically, either as conjugates with a toxin or therapeutic agent, or as naked antibodies capable of inhibiting cell proliferation or function.

109P1 D4 antibodies can be introduced into a patient such'that the antibody binds to 109P1D4 and modulates a function, such as an interaction with a binding partner, and consequently mediates destruction of the tumor cells and/or inhibits the growth of the tumor cells. Mechanisms by which such antibodies exert a therapeutic effect can include complement-mediated cytolysis, antibody-dependent cellular cytotoxicity, modulation of the physiological function of 109P1 D4, inhibition of ligand binding or signal transduction pathways, modulation of tumor cell differentiation, alteration of tumor angiogenesis factor profiles, and/or apoptosis.

Those skilled in the art understand that antibodies can be used to specifically target and bind immunogenic molecules such as an immunogenic region of a 109P1 D4 sequence shown in Figure 2 or Figure 3. In addition, skilled artisans understand that it is routine to conjugate antibodies to cytotoxic agents (see, e. g., Slevers et al. Blood 93 : 11 3678- 3684 (June 1, 1999)). When cytotoxic and/or therapeutic agents are delivered directly to cells, such as by conjugating them to antibodies specific for a molecule expressed by that cell (e. g. 109PI D4), the cytotoxic agent will exert its known biological effect (i. e. cytotoxicity) on those cells.

A wide variety of compositions and methods for using antibody-cytotoxic agent conjugates to kill cells are known in the art. In the context of cancers, typical methods entail administering to an animal having a tumor a biologically effective amount of a conjugate comprising a selected cytotoxic and/or therapeutic agent linked to a targeting agent (e. g. an anti- 109P1 D4 antibody) that binds to a marker (e. g. 109P1 D4) expressed, accessible to binding or localized on the cell surfaces.

A typical embodiment is a method of delivering a cytotoxic and/or therapeutic agent to a cell expressing 109P1D4, comprising conjugating the cytotoxic agent to an antibody that immunospecifically binds to a 109P1 D4 epitope, and, exposing the cell to the antibody-agent conjugate. Another illustrative embodiment is a method of treating an individual suspected of suffering from metastasized cancer, comprising a step of administering parenterally to said individual a pharmaceutical composition comprising a therapeutically effective amount of an antibody conjugated to a cytotoxic and/or therapeutic agent.

Cancer immunotherapy using anti-109P1D4 antibodies can be done in accordance with various approaches that have been successfully employed in the treatment of other types of cancer, including but not limited to colon cancer (Arlen et al., 1998, Crit. Rev. Immunol. 18 : 133-138), multiple myeloma (Ozaki et al., 1997, Blood 90 : 3179-3186, Tsunenari et al., 1997, Blood 90 : 2437-2444), gastric cancer (Kasprzyk et al., 1992, Cancer Res. 52 : 2771-2776), B-cell lymphoma (Funakoshi et al., 1996, J. Immunother. Emphasis Tumor Immunol. 19 : 93-101), leukemia (Zhong et al., 1996, Leuk. Res. 20 : 581-589), colorectal cancer (Moun et al., 1994, Cancer Res. 54 : 6160-6166 ; Velders et aL, 1995, Cancer Res. 55 : 4398-4403), and breast cancer (Shepard et al., 1991, J. Clin. Immunol. 11 : 117-127). Some therapeutic approaches involve conjugation of naked antibody to a toxin or radioisotope, such as the conjugation ofY or i to anti-CD20 antibodies (e. g., ZevalinTM, IDEC Pharmaceuticals Corp. or Bexxar, Coulter Pharmaceutical), while others involve co-administration of antibodies and other therapeutic agents, such as HerceptinTM (trastuzumab) with paclitaxel (Genentech, Inc.). The antibodies can be conjugated to a therapeutic agent. To treat prostate cancer, for example, 109P1D4 antibodies can be administered in conjunction with radiation, chemotherapy or hormone ablation. Also, antibodies can be conjugated to a toxin such as calicheamicin (e. g., Mylotarg, Wyeth-Ayerst, Madison, NJ, a recombinant humanized IgG4 kappa antibody conjugated to antitumor antibiotic calicheamicin) or a maytansinoid (e. g., taxane-based Tumor-Activated Prodrug, TAP, platform, ImmunoGen, Cambridge, MA, also see e. g., US Patent 5, 416, 064).

Although 109P1 D4 antibody therapy is useful for all stages of cancer, antibody therapy can be particularly appropriate in advanced or metastatic cancers. Treatment with the antibody therapy of the invention is indicated for patients who have received one or more rounds of chemotherapy. Alternatively, antibody therapy of the invention is combined with a chemotherapeutic or radiation regimen for patients who have not received chemotherapeutic treatment. Additionally, antibody therapy can enable the use of reduced dosages of concomitant chemotherapy, particularly for patients who do not tolerate the toxicity of the chemotherapeutic agent very well. Fan et al. (Cancer Res. 53 : 4637-4642, 1993), Prewett et al.

(International J. of Onco. 9 : 217-224, 1996), and Hancock et al. (Cancer Res. 51 : 4575-4580, 1991) describe the use of various antibodies together with chemotherapeutic agents.

Although 109P1 D4 antibody therapy is useful for all stages of cancer, antibody therapy can be particularly appropriate in advanced or metastatic cancers. Treatment with the antibody therapy of the invention is indicated for patients who have received one or more rounds of chemotherapy. Alternatively, antibody therapy of the invention is combined with a chemotherapeutic or radiation regimen for patients who have not received chemotherapeutic treatment. Additionally, antibody therapy can enable the use of reduced dosages of concomitant chemotherapy, particularly for patients who do not tolerate the toxicity of the chemotherapeutic agent very well.

Cancer patients can be evaluated for the presence and level of 109P1D4 expression, preferably using immunohistochemical assessments of tumor tissue, quantitative 109P1 D4 imaging, or other techniques that reliably indicate the presence and degree of 109P1 D4 expression, immunohistochemicai analysis of tumor biopsies or surgical specimens is preferred for this purpose. Methods for immunohistochemical analysis of tumor tissues are well known in the art.

Anti-109P1 D4 monoclonal antibodies that treat prostate and other cancers include those that initiate a potent immune response against the tumor or those that are directly cytotoxic. In this regard, anti-109P1 D4 monoclonal antibodies (mAbs) can elicit tumor cell lysis by either complement-mediated or antibody-dependent cell cytotoxicity (ADCC) mechanisms, both of which require an intact Fc portion of the immunoglobulin molecule for interaction with effector cell Fc receptor sites on complement proteins. In addition, anti-109P1 D4 mAbs that exert a direct biological effect on tumor growth are useful to treat cancers that express 109P1 D4. Mechanisms by which directly cytotoxic mAbs act include : inhibition of cell growth, modulation of cellular differentiation, modulation of tumor angiogenesis factor profiles, and the induction of apoptosis.

The mechanism (s) by which a particular anti-109P1 D4 mAb exerts an anti-tumor effect is evaluated using any number of in vitro assays that evaluate cell death such as ADCC, ADMMC, complement-mediated cell lysis, and so forth, as is generally known in the art.

In some patients, the use of murine or other non-human monoclonal antibodies, or human/mouse chimeric mAbs can induce moderate to strong immune responses against the non-human antibody. This can result in clearance of the antibody from circulation and reduced efficacy. In the most severe cases, such an immune response can lead to the extensive formation of immune complexes which, potentially, can cause renal failure. Accordingly, preferred monoclonal antibodies used in the therapeutic methods of the invention are those that are either fully human or humanized and that bind specifically to the target 109P1 D4 antigen with high affinity but exhibit low or no antigenicity in the patient.

Therapeutic methods of the invention contemplate the administration of single anti-109P1 D4 mAbs as well as combinations, or cocktails, of different mAbs. Such mAb cocktails can have certain advantages inasmuch as they contain mAbs that target different epitopes, exploit different effector mechanisms or combine directly cytotoxic mAbs with mAbs that rely on immune effector functionality. Such mAbs in combination can exhibit synergistic therapeutic effects. In addition, anti- 109P1 D4 mAbs can be administered concomitantly with other therapeutic modalities, including but not limited to various chemotherapeutic agents, androgen-blockers, immune modulators (e. g., IL-2, GM-CSF), surgery or radiation. The anti- 109P1 D4 mAbs are administered in their"naked"or unconjugated form, or can have a therapeutic agent (s) conjugated to them.

Anti-109P1 D4 antibody formulations are administered via any route capable of delivering the antibodies to a tumor cell. Routes of administration include, but are not limited to, intravenous, intraperitoneal, intramuscular, intratumor, intradermal, and the like. Treatment generally involves repeated administration of the anti-109P1 D4 antibody preparation, via an acceptable route of administration such as intravenous injection (IV), typically at a dose in the range of about 0. 1,. 2, . 3,. 4,. 5,. 6,. 7,. 8,. 9., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, or 25 mg/kg body weight. In general, doses in the range of 10-1000 mg mAb per week are effective and well tolerated.

Based on clinical experience with the-derceptinz mAb in the treatment of metastatic breast cancer, an initial loading dose of approximately 4 mg/kg patient body weight IV, followed by weekly doses of about 2 mg/kg IV of the anti- 109P1D4 mAb preparation represents an acceptable dosing regimen. Preferably, the initial loading dose is administered as a 90-minute or longer infusion. The periodic maintenance dose is administered as a 30 minute or longer infusion, provided the initial dose was well tolerated. As appreciated by those of skill in the art, various factors can influence the ideal dose regimen in a particular case. Such factors include, for example, the binding affinity and half life of the Ab or mAbs used, the degree of 109P1 D4 expression in the patient, the extent of circulating shed 109P1 D4 antigen, the desired steady-state antibody concentration level, frequency of treatment, and the influence of chemotherapeutic or other agents used in combination with the treatment method of the invention, as well as the health status of a particular patient.

Optionally, patients should be evaluated for the levels of 109P1D4 in a given sample (e. g. the levels of circulating 109P1D4 antigen andlor 109P1D4 expressing cells) in order to assist in the determination of the most effective dosing regimen, etc. Such evaluations are also used for monitoring purposes throughout therapy, and are useful to gauge therapeutic success in combination with the evaluation of other parameters (for example, urine cytology and/or lmmunoCyt levels in bladder cancer therapy, or by analogy, serum PSA levels in prostate cancer therapy).

Anti-idiotypic anti-109P1 D4 antibodies can also be used in anti-cancer therapy as a vaccine for inducing an immune response to cells expressing a 109P1D4-related protein. In particular, the generation of anti-idiotypic antibodies is well known in the art ; this methodology can readily be adapted to generate anti-idiotypic anti-109P1 D4 antibodies that mimic an epitope on a 109P1 D4-related protein (see, for example, Wagner et al., 1997, Hybridoma 16 : 33-40 ; Foon et al., 1995, J.

Clin. Invest. 96 : 334-342 ; Herlyn et al., 1996, Cancer Immunol. mmunother. 43 : 65-76). Such an anti-idiotypic antibody can be used in cancer vaccine strategies.

X. C.) 109P1D4 as a Target for Cellular Immune Responses Vaccines and methods of preparing vaccines that contain an immunogenically effective amount of one or more HLA-binding peptides as described herein are further embodiments of the invention. Furthermore, vaccines in accordance with the invention encompass compositions of one or more of the claimed peptides. A peptide can be present in a vaccine individually. Alternatively, the peptide can exist as a homopolymer comprising multiple copies of the same peptide, or as a heteropolymer of various peptides. Polymers have the advantage of increased immunological reaction and, where different peptide epitopes are used to make up the polymer, the additional ability to induce antibodies and/or CTLs that react with different antigenic determinants of the pathogenic organism or tumor-related peptide targeted for an immune response. The composition can be a naturally occurring region of an antigen or can be prepared, e. g., recombinantly or by chemical synthesis.

Carriers that can be used with vaccines of the invention are well known in the art, and include, e. g., thyroglobulin, albumins such as human serum albumin, tetanus toxoid, polyamino acids such as poly L-lysine, poly L-glutamic acid, influenza, hepatitis B virus core protein, and the like. The vaccines can contain a physiologically tolerable (i. e., acceptable) diluent such as water, or saline, preferably phosphate buffered saline. The vaccines also typically include an adjuvant.

Adjuvants such as incomplete Freund's adjuvant, aluminum phosphate, aluminum hydroxide, or alum are examples of materials well known in the art. Additionally, as disclosed herein, CTL responses can be primed by conjugating peptides of the invention to lipids, such as tripalmitoyl-S-glycerylcysteinlyseryl- serine (PsCSS). Moreover, an adjuvant such as a synthetic cytosine-phosphorothiolated-guanine-containing (CpG) oligonucleotides has been found to increase CTL responses 10-to 100-fold. (see, e. g. Davila and Celis, J. Immunol. 165 : 539-547 (2000)) Upon immunization with a peptide composition in accordance with the invention, via injection, aerosol, oral, transdermal, transmucosal, intrapleural, intrathecal, or other suitable routes, the immune system of the host responds to the vaccine by producing large amounts of CTLs and/or HTLs specific for the desired antigen. Consequently, the host becomes at least partially immune to later development of cells that express or overexpress 109P1D4 antigen, or derives at least some therapeutic benefit when the antigen was tumor-associated.

In some embodiments, it may be desirable to combine the class I peptide components with components that induce or facilitate neutralizing antibody and or helper T cell responses directed to the target antigen. A preferred embodiment of such a composition comprises class I and class II epitopes in accordance with the invention. An alternative embodiment of such a composition comprises a ciass) and/or ciass ii epitope in accordance with the invention, along with a cross reactive HTL epitope such as PADRE (Epimmune, San Diego, CA) molecule (described e. g., in U. S. Patent Number 5, 736, 142).

A vaccine of the invention can also include antigen-presenting cells (APC), such as dendritic cells (DC), as a vehicle to present peptides of the invention. Vaccine compositions can be created in vitro, following dendritic cell mobilization and harvesting, whereby loading of dendritic cells occurs in vitro. For example, dendritic cells are transfected, e. g., with a minigene in accordance with the invention, or are pulsed with peptides. The dendritic cell can then be administered to a patient to elicit immune responses in vivo. Vaccine compositions, either DNA-or peptide-based, can also be administered in vivo in combination with dendritic cell mobilization whereby loading of dendritic cells occurs in vivo.

Preferably, the following principles are utilized when selecting an array of epitopes for inclusion in a polyepitopic composition for use in a vaccine, or for selecting discrete epitopes to be included in a vaccine and/or to be encoded by nucleic acids such as a minigene. It is preferred that each of the following principles be balanced in order to make the selection. The multiple epitopes to be incorporated in a given vaccine composition may be, but need not be, contiguous in sequence in the native antigen from which the epitopes are derived.

1.) Epitopes are selected which, upon administration, mimic immune responses that have been observed to be correlated with tumor clearance. For HLA Class I this includes 3-4 epitopes that come from at least one tumor associated antigen (TAA). For HLA Class II a similar rationale is employed ; again 3-4 epitopes are selected from at least one TAA (see, e. g., Rosenberg et al., Science 278 : 1447-1450). Epitopes from one TAA may be used in combination with epitopes from one or more additional TAAs to produce a vaccine that targets tumors with varying expression patterns of frequently-expressed TAAs.

2.) Epitopes are selected that have the requisite binding affinity established to be correlated with immunogenicity : for HLA Class I an ICso of 500 nM or less, often 200 nM or less ; and for Class 11 an ICso of 1000 nM or less.

3.) Sufficient supermotif bearing-peptides, or a sufficient array of allele-specific motif-bearing peptides, are selected to give broad population coverage. For example, it is preferable to have at least 80% population coverage. A Monte Carlo analysis, a statistical evaluation known in the art, can be employed to assess the breadth, or redundancy of, population coverage.

4.) When selecting epitopes from cancer-related antigens it is often useful to select analogs because the patient may have developed tolerance to the native epitope.

5.) Of particular relevance are epitopes referred to as"nested epitopes."Nested epitopes occur where at least two epitopes overlap in a given peptide sequence. A nested peptide sequence can comprise B cell, HLA class I and/or HLA class II epitopes. When providing nested epitopes, a general objective is to provide the greatest number of epitopes per sequence. Thus, an aspect is to avoid providing a peptide that is any longer than the amino terminus of the amino terminal epitope and the carboxyl terminus of the carboxyl terminal epitope in the peptide. When providing a multi-epitopic sequence, such as a sequence comprising nested epitopes, it is generally important to screen the sequence in order to insure that it does not have pathological or other deleterious biological properties.

6.) If a polyepitopic protein is created, or when creating a minigene, an objective is to generate the smallest peptide that encompasses the epitopes of interest. This principle is similar, if not the same as that employed when selecting a peptide comprising nested epitopes. However, with an artificial polyepitopic peptide, the size minimization objective is balanced against the need to integrate any spacer sequences between epitopes in the polyepitopic protein. Spacer amino acid residues can, for example, be introduced to avoid junctional epitopes (an epitope recognized by the immune system, not present in the target antigen, and only created by the man-made juxtaposition of epitopes), or to facilitate cleavage between epitopes and thereby enhance epitope presentation. Junctional epitopes are generally to be avoided because the recipient may generate an immune response to that non-native epitope. Of particular concern is a junctional epitope that is a "dominant epitope."A dominant epitope may lead to such a zealous response that immune responses to other epitopes are diminished or suppressed.

7.) Where the sequences of multiple variants of the same target protein are present, potential peptide epitopes can also be selected on the basis of their conservancy. For example, a criterion for conservancy may define that the entire sequence of an HLA class I binding peptide or the entire 9-mer core of a class 11 binding peptide be conserved in a designated percentage of the sequences evaluated for a specific protein antigen.

X. C. 1. MinigeneVaccines A number of different approaches are available which allow simultaneous delivery of multiple epitopes. Nucleic acids encoding the peptides of the invention are a particularly useful embodiment of the invention. Epitopes for inclusion in a minigene are preferably selected according to the guidelines set forth in the previous section. A preferred means of administering nucleic acids encoding the peptides of the invention uses minigene constructs encoding a peptide comprising one or multiple epitopes of the invention.

The use of multi-epitope minigenes is described below and in, ishioka et al., J. Immunol. 162 : 3915-3925, 1999 ; An, L. and Whitton, J. L., J. Virol. 71 : 2292, 1997 ; Thomson, S. A. et al., J. Immunol. 157 : 822, 1996 ; Whitton, J. L. et al., J. Virol.

67 : 348, 1993 ; Hanke, R. et al., Vaccine 16 : 426, 1998. For example, a multi-epitope DNA plasmid encoding supermotif- and/or motif-bearing epitopes derived 109P1D4, the PADRE@ universal helper T cell epitope or multiple HTL epitopes from 109P1 D4 (see e. g., Tables Vlil-XXl and XXII to XLIX), and an endopiasmic reticulum-translocating signal sequence can be engineered. A vaccine may also comprise epitopes that are derived from other TAAs.

The immunogenicity of a multi-epitopic minigene can be confirmed in transgenic mice to evaluate the magnitude of CTL induction responses against the epitopes tested. Further, the immunogenicity of DNA-encoded epitopes in vivo can be correlated with the in vitro responses of specific CTL lines against target cells transfected with the DNA plasmid. Thus, these experiments can show that the minigene serves to both : 1.) generate a CTL response and 2.) that the induced CTLs recognized cells expressing the encoded epitopes.

For example, to create a DNA sequence encoding the selected epitopes (minigene) for expression in human cells, the amino acid sequences of the epitopes may be reverse translated. A human codon usage table can be used to guide the codon choice for each amino acid. These epitope-encoding DNA sequences may be directly adjoined, so that when translated, a continuous polypeptide sequence is created. To optimize expression and/or immunogenicity, additional elements can be incorporated into the minigene design. Examples of amino acid sequences that can be reverse translated and included in the minigene sequence include : HLA class I epitopes, HLA class 11 epitopes, antibody epitopes, a ubiquitination signal sequence, and/or an endoplasmic reticulum targeting signal. In addition, HLA presentation of CTL and HTL epitopes may be improved by including synthetic (e. g. poly-alanine) or naturally-occurring flanking sequences adjacent to the CTL or HTL epitopes ; these larger peptides comprising the epitope (s) are within the scope of the invention.

The minigene sequence may be converted to DNA by assembling oligonucleotides that encode the plus and minus strands of the minigene. Overlapping oligonucleotides (30-100 bases long) may be synthesized, phosphorylated, purified and annealed under appropriate conditions using well known techniques. The ends of the oligonucleotides can be joined, for example, using T4 DNA ligase. This synthetic minigene, encoding the epitope polypeptide, can then be cloned into a desired expression vector.

Standard regulatory sequences well known to those of skill in the art are preferably included in the vector to ensure expression in the target cells. Several vector elements are desirable : a promoter with a down-stream cloning site for minigene insertion ; a polyadenylation signal for efficient transcription termination ; an E coli origin of replication ; and an E coli selectable marker (e. g. ampicillin or kanamycin resistance). Numerous promoters can be used for this purpose, e. g., the human cytomegalovirus (hCMV) promoter. See, e. g., U. S. Patent Nos. 5, 580, 859 and 5, 589, 466 for other suitable promoter sequences.

Additional vector modifications may be desired to optimize minigene expression and immunogenicity. In some cases, introns are required for efficient gene expression, and one or more synthetic or naturally-occurring introns could be incorporated into the transcribed region of the minigene. The inclusion of mRNA stabilization sequences and sequences for replication in mammalian cells may also be considered for increasing minigene expression.

Once an expression vector is selected, the minigene is cloned into the polylinker region downstream of the promoter. This plasmid is transformed into an appropriate E coli strain, and DNA is prepared using standard techniques.

The orientation and DNA sequence of the minigene, as well as all other elements included in the vector, are confirmed using restriction mapping and DNA sequence analysis. Bacterial cells harboring the correct plasmid can be stored as a master cell bank and a working cell bank.

In addition, immunostimulatory sequences (ISSs or CpGs) appear to play a role in the immunogenicity of DNA vaccines. These sequences may be included in the vector, outside the minigene coding sequence, if desired to enhance immunogenicity.

In some embodiments, a bi-cistronic expression vector which allows production of both the minigene-encoded epitopes and a second protein (included to enhance or decrease immunogenicity) can be used. Examples of proteins or polypeptides that could beneficially enhance the immune response if co-expressed include cytokines (e. g., IL-2, IL-1 2, GM- CSF), cytokine-inducing molecules (e. g., LeIF), costimulatory molecules, or for HTL responses, pan-DR binding proteins (PADRE, Epimmune, San Diego, CA). Helper (HTL) epitopes can be joined to intracellular targeting signals and expressed separately from expressed CTL epitopes ; this allows direction of the HTL epitopes to a cell compartment different than that of the CTL epitopes. If required, this could facilitate more efficient entry of HTL epitopes into the HLA class it pathway, thereby improving HTL induction. In contrast to HTL or CTL induction, specifically decreasing the immune response by co-expression of immunosuppressive molecules (e. g. TGF-, 8) may be beneficial in certain diseases.

Therapeutic quantities of plasmid DNA can be produced for example, by fermentation in E coli, followed by purification. Aliquots from the working cell bank are used to inoculate growth medium, and grown to saturation in shaker flasks or a bioreactor according to well-known techniques. Plasmid DNA can be purified using standard bioseparation technologies such as solid phase anion-exchange resins supplied by QIAGEN, Inc. (Valencia, California). If required, supercoiled DNA can be isolated from the open circular and linear forms using gel electrophoresis or other methods.

Purified plasmid DNA can be prepared for injection using a variety of formulations. The simplest of these is reconstitution of lyophilized DNA in sterile phosphate-buffer saline (PBS). This approach, known as"naked DNA,"is currently being used for intramuscular (IM) administration in clinical trials. To maximize the immunotherapeutic effects of minigene DNA vaccines, an alternative method for formulating purified plasmid DNA may be desirable. A variety of methods have been described, and new techniques may become available. Cationic lipids, glycolipids, and fusogenic liposomes can also be used in the formulation (see, e. g., as described by WO 93/24640 ; Mannino & Gould-Fogerite, BioTechniques 6 (7) : 682 (1988) ; U. S. Pat No. 5, 279, 833 ; WO 91/06309 ; and Feigne, et al., Proc. Nat7 Acad. Sci. USA 84 : 7413 (1987). In addition, peptides and compounds referred to collectively as protective, interactive, non-condensing compounds (PINC) could also be complexed to purified plasmid DNA to influence variables such as stability, intramuscular dispersion, or trafficking to specific organs or cell types.

Target cell sensitization can be used as a functional assay for expression and HLA class I presentation of minigene-encoded CTL epitopes. For example, the plasmid DNA is introduced into a mammalian cell line that is suitable as a target for standard CTL chromium release assays. The transfection method used will be dependent on the final formulation. Electroporation can be used for"naked"DNA, whereas cationic lipids allow direct in vitro transfection. A plasmid expressing green fluorescent protein (GFP) can be co-transfected to allow enrichment of transfected cells using fluorescence activated cell sorting (FACS). These cells are then chromium-51 (srCr) labeled and used as target cells for epitope-specific CTL lines ; cytolysis, detected by 5aCr release, indicates both production of, and HLA presentation of, minigene-encoded CTL epitopes. Expression of HTL epitopes may be evaluated in an analogous manner using assays to assess HTL activity.

In vivo immunogenicity is a second approach for functional testing of minigene DNA formulations. Transgenic mice expressing appropriate human HLA proteins are immunized with the DNA product. The dose and route of administration are formulation dependent (e. g., IM for DNA in PBS, intraperitoneal (i. p.) for lipid-complexed DNA). Twenty-one days after immunization, splenocytes are harvested and restimulated for one week in the presence of peptides encoding each epitope being tested. Thereafter, for CTL effector cells, assays are conducted for cytolysis of peptide-loaded, srCr-labeled target cells using standard techniques. Lysis of target cells that were sensitized by HLA loaded with peptide epitopes, corresponding to minigene-encoded epitopes, demonstrates DNA vaccine function for in vivo induction of CTLs.

Immunogenicity of HTL epitopes is confirmed in transgenic mice in an analogous manner.

Alternatively, the nucleic acids can be administered using ballistic delivery as described, for instance, in U. S.

Patent No. 5, 204, 253. Using this technique, particles comprised solely of DNA are administered. In a further alternative embodiment, DNA can be adhered to particles, such as gold particles.

Minigenes can also be delivered using other bacterial or viral delivery systems well known in the art, e. g., an expression construct encoding epitopes of the invention can be incorporated into a viral vector such as vaccinia.

X. C. 2. Combinations of CTL Peptides with Helper Peptides Vaccine compositions comprising CTL peptides of the invention can be modified, e. g., analoged, to provide desired attributes, such as improved serum half life, broadened population coverage or enhanced immunogenicity.

For instance, the ability of a peptide to induce CTL activity can be enhanced by linking the peptide to a sequence which contains at least one epitope that is capable of inducing a T helper cell response. Although a CTL peptide can be directly linked to a T helper peptide, often CTL epitope/HTL epitope conjugates are linked by a spacer molecule. The spacer is typically comprised of relatively small, neutral molecules, such as amino acids or amino acid mimetics, which are substantially uncharged under physiological conditions. The spacers are typically selected from, e. g., Ala, Gly, or other neutral spacers of nonpolar amino acids or neutral polar amino acids. It will be understood that the optionally present spacer need not be comprised of the same residues and thus may be a hetero-or homo-oligomer. When present, the spacer will usually be at least one or two residues, more usually three to six residues and sometimes 10 or more residues. The CTL peptide epitope can be linked to the T helper peptide epitope either directly or via a spacer either at the amino or carboxy terminus of the CTL peptide. The amino terminus of either the immunogenic peptide or the T helper peptide may be acylated.

In certain embodiments, the T helper peptide is one that is recognized by T helper cells present in a majority of a genetically diverse population. This can be accomplished by selecting peptides that bind to many, most, or all of the HLA class II molecules. Examples of such amino acid bind many HLA Class II molecules include sequences from antigens such as tetanus toxoid at positions 830-843 QYIKANSKFIGITE ; (SEQ ID NO : 40), Plasmodium falciparum circumsporozoite (CS) protein at positions 378-398 DIEKKIAKMEKASSVFNWNS ; (SEQ ID NO : 41), and Streptococcus 18kD protein at positions 116-131 GAVDSILGGVATYGAA ; (SEQ ID NO : 42). Other examples include peptides bearing a DR 1-4-7 supermotif, or either of the DR3 motifs.

Alternatively, it is possible to prepare synthetic peptides capable of stimulating T helper lymphocytes, in a loosely HLA-restricted fashion, using amino acid sequences not found in nature (see, e. g., PCT publication WO 95/07707). These synthetic compounds called Pan-DR-binding epitopes (e. g., PADRE, Epimmune, Inc., San Diego, CA) are designed, most preferably, to bind most HLA-DR (human HLA class it) molecules. For instance, a pan-DR-binding epitope peptide having the formula : xKXVAAWTLKAAx (SEQ 1D NO : 43), where"X"is either cyclohexylalanine, phenylalanine, or tyrosine, and a is either D-alanine or L-alanine, has been found to bind to most HLA-DR alleles, and to stimulate the response of T helper lymphocytes from most individuals, regardless of their HLA type. An alternative of a pan-DR binding epitope comprises all "natural amino acids and can be provided in the form of nucleic acids that encode the epitope.

HTL peptide epitopes can also be modified to alter their biological properties. For example, they can be modified to include D-amino acids to increase their resistance to proteases and thus extend their serum half life, or they can be conjugated to other molecules such as iipids, proteins, carbohydrates, and the like to increase their biological activity. For example, a T helper peptide can be conjugated to one or more palmitic acid chains at either the amino or carboxyl termini.

X. C. 3. Combinations of CTL Peptides with T Cell Priming Agents In some embodiments it may be desirable to include in the pharmaceutical compositions of the invention at least one component which primes B lymphocytes or T lymphocytes. Lipids have been identified as agents capable of priming CTL in vivo. For example, palmitic acid residues can be attached to the s-and a-amino groups of a lysine residue and then linked, e. g., via one or more linking residues such as Gly, Gly-Gly-, Ser, Ser-Ser, or the like, to an immunogenic peptide.

The lipidated peptide can then be administered either directly in a micelle or particle, incorporated into a liposome, or emulsified in an adjuvant, e. g., incomplete Freund's adjuvant. In a preferred embodiment, a particularly effective immunogenic composition comprises palmitic acid attached to e-and a-amino groups of Lys, which is attached via linkage, e. g., Ser-Ser, to the amino terminus of the immunogenic peptide.

As another example of lipid priming of CTL responses, E. coli lipoproteins, such as tripalmitoyl-S- glycerylcysteinlyseryl-serine (P3CSS) can be used to prime virus specific CTL when covalently attached to an appropriate peptide (see, e. g., Deres, et al., Nature 342 : 561, 1989). Peptides of the invention can be coupled to P3CSS, for example, and the lipopeptide administered to an individual to prime specifically an immune response to the target antigen. Moreover, because the induction of neutralizing antibodies can also be primed with P3CSS-conjugated epitopes, two such compositions can be combined to more effectively elicit both humoral and cell-mediated responses.

X. C, 4. Vaccine Compositions Comprising DC Pulsed with CTL and/or HTL Peptides An embodiment of a vaccine composition in accordance with the invention comprises ex vivo administration of a cocktail of epitope-bearing peptides to PBMC, or isolated DC therefrom, from the patient's blood. A pharmaceutical to facilitate harvesting of DC can be used, such as Progenipoietin (Pharmacia-Monsanto, St. Louis, MO) or GM-CSF/IL-4.

After pulsing the DC with peptides and prior to infusion into patients, the DC are washed to remove unbound peptides. In this embodiment, a vaccine comprises peptide-pulsed DCs which present the pulsed peptide epitopes complexed with HLA molecules on their surfaces.

The DC can be pulsed ex vivo with a cocktail of peptides, some of which stimulate CTL responses to 109P1D4. optionally, a helper T cell (HTL) peptide, such as a natural or artificial loosely restricted HLA Class II peptide, can be included to facilitate the CTL response. Thus, a vaccine in accordance with the invention is used to treat a cancer which expresses or overexpresses 109P1 D4.

X. D. Adoptive Immunotherapy Antigenic 1 09P1 D4-related peptides are used to elicit a CTL and/or HTL response ex vivo, as well. The resulting CTL or HTL cells, can be used to treat tumors in patients that do not respond to other conventional forms of therapy, or will not respond to a therapeutic vaccine peptide or nucleic acid in accordance with the invention. Ex vivo CTL or HTL responses to a particular antigen are induced by incubating in tissue culture the patient's, or genetically compatible, CTL or HTL precursor cells together with a source of antigen-presenting cells (APC), such as dendritic cells, and the appropriate immunogenic peptide. After an appropriate incubation time (typically about 7-28 days), in which the precursor cells are activated and expanded into effector cells, the cells are infused back into the patient, where they will destroy (CTL) or facilitate destruction (HTL) of their specific target cell (e. g., a tumor cell). Transfected dendritic cells may also be used as antigen presenting cells.

X. E. Administration of Vaccines for Therapeutic or Prophylactic Purposes Pharmaceutical and vaccine compositions of the invention are typically used to treat and/or prevent a cancer that expresses or overexpresses 109P1 D4. In therapeutic applications, peptide and/or nucleic acid compositions are administered to a patient in an amount sufficient to elicit an effective B cell, CTL and/or HTL response to the antigen and to cure or at least partially arrest or slow symptoms and/or complications. An amount adequate to accomplish this is defined as "therapeutically effective dose."Amounts effective for this use will depend on, e. g., the particular composition administered, the manner of administration, the stage and severity of the disease being treated, the weight and general state of health of the patient, and the judgment of the prescribing physician.

For pharmaceutical compositions, the immunogenic peptides of the invention, or DNA encoding them, are generally administered to an individual already bearing a tumor that expresses 109PI D4. The peptides or DNA encoding them can be administered individually or as fusions of one or more peptide sequences. Patients can be treated with the immunogenic peptides separately or in conjunction with other treatments, such as surgery, as appropriate.

For therapeutic use, administration should generally begin at the first diagnosis of 109P1 D4-associated cancer.

This is followed by boosting doses until at least symptoms are substantially abated and for a period thereafter. The embodiment of the vaccine composition (i. e., including, but not limited to embodiments such as peptide cocktails, polyepitopic polypeptides, minigenes, or TAA-specific CTLs or pulsed dendritic cells) delivered to the patient may vary according to the stage of the disease or the patient's health status. For example, in a patient with a tumor that expresses 109P1 D4, a vaccine comprising 109P1 D4-specific CTL may be more efficacious in killing tumor cells in patient with advanced disease than alternative embodiments.

It is generally important to provide an amount of the peptide epitope delivered by a mode of administration sufficient to stimulate effectively a cytotoxic T cell response ; compositions which stimulate helper T cell responses can also be given in accordance with this embodiment of the invention.

The dosage for an initial therapeutic immunization generally occurs in a unit dosage range where the lower value is about 1, 5, 50, 500, or 1, 000 pg and the higher value is about 10, 000 ; 20, 000 ; 30, 000 ; or 50, 000 pg. Dosage values for a human typically range from about 500 pg to about 50, 000 pg per 70 kilogram patient. Boosting dosages of between about 1. 0 jig to about 50, 000 p. g of peptide pursuant to a boosting regimen over weeks to months may be administered depending upon the patient's response and condition as determined by measuring the specific activity of CTL and HTL obtained from the patient's blood. Administration should continue until at least clinical symptoms or laboratory tests indicate that the neoplasia, has been eliminated or reduced and for a period thereafter. The dosages, routes of administration, and dose schdules are adjusted in accordance with methodologies known in the art.

In certain embodiments, the peptides and compositions of the present invention are employed in serious disease states, that is, life-threatening or potentially life threatening situations. In such cases, as a result of the minimal amounts of extraneous substances and the relative nontoxic nature of the peptides in preferred compositions of the invention, it is possible and may be felt desirable by the treating physician to administer substantial excesses of these peptide compositions relative to these stated dosage amounts.

The vaccine compositions of the invention can also be used purely as prophylactic agents. Generally the dosage for an initial prophylactic immunization generally occurs in a unit dosage range where the lower value is about 1, 5, 50, 500, or 1000 pg and the higher value is about 10, 000 ; 20, 000 ; 30, 000 ; or 50, 000 u9. Dosage values for a human typically range from about 500 pg to about 50, 000 nu per 70 kilogram patient. This is followed by boosting dosages of between about 1. 0 jig to about 50, 000 jl9 of peptide administered at defined intervals from about four weeks to six months after the initial administration of vaccine. The immunogenicity of the vaccine can be assessed by measuring the specific activity of CTL and HTL obtained from a sample of the patient's blood.

The pharmaceutical compositions for therapeutic treatment are intended for parenteral, topical, oral, nasal, intrathecal, or local (e. g. as a cream or topical ointment) administration. Preferably, the pharmaceutical compositions are administered parentally, e. g., intravenously, subcutaneously, intradermally, or intramuscularly. Thus, the invention provides compositions for parenteral administration which comprise a solution of the immunogenic peptides dissolved or suspended in an acceptable carrier, preferably an aqueous carrier.

A variety of aqueous carriers may be used, e. g., water, buffered water, 0. 8% saline, 0. 3% glycine, hyaluronic acid and the like. These compositions may be sterilized by conventional, well-known sterilization techniques, or may be sterile filtered. The resulting aqueous solutions may be packaged for use as is, or lyophilized, the lyophilized preparation being combined with a sterile solution prior to administration.

The compositions may contain pharmaceutical acceptable auxiliary substances as required to approximate physiological conditions, such as pH-adjusting and buffering agents, tonicity adjusting agents, wetting agents, preservatives, and the like, for example, sodium acetate, sodium lactate, sodium chloride, potassium chloride, calcium chloride, sorbitan monolaurate, triethanolamine oleate, etc.

The concentration of peptides of the invention in the pharmaceutical formulations can vary widely, i. e., from less than about 0. 1 %, usually at or at least about 2% to as much as 20% to 50% or more by weight, and will be selected primarily by fluid volumes, viscosities, etc., in accordance with the particular mode of administration selected.

A human unit dose form of a composition is typically included in a pharmaceutical composition that comprises a human unit dose of an acceptable carrier, in one embodiment an aqueous carrier, and is administered in a volume/quantity that is known by those of skill in the art to be used for administration of such compositions to humans (see, e. g., Remington's Pharmaceutical Sciences, 17 Edition, A. Gennaro, Editor, Mack Publishing Co., Easton, Pennsylvania, 1985). For example a peptide dose for initial immunization can be from about 1 to about 50, 000 lg, generally 100-5, 000 gag, for a 70 kg patient.

For example, for nucleic acids an initial immunization may be performed using an expression vector in the form of naked nucleic acid administered IM (or SC or ID) in the amounts of 0. 5-5 mg at multiple sites. The nucleic acid (0. 1 to 1000 p. g) can also be administered using a gene gun. Following an incubation period of 3-4 weeks, a booster dose is then administered. The booster can be recombinant fowlpox virus administered at a dose of 5-107 to 5x109 pfu.

For antibodies, a treatment generally involves repeated administration of the anti-109P1D4 antibody preparation, via an acceptable route of administration such as intravenous injection (fV), typically at a dose in the range of about 0. 1 to about 10 mg/kg body weight. In general, doses in the range of 10-500 mg mAb per week are effective and well tolerated.

Moreover, an initial loading dose of approximately 4 mg/kg patient body weight IV, followed by weekly doses of about 2 mg/kg IV of the anti-109P1 D4 mAb preparation represents an acceptable dosing regimen. As appreciated by those of skill in the art, various factors can influence the ideal dose in a particular case. Such factors include, for example, half life of a composition, the binding affinity of an Ab, the immunogenicity of a substance, the degree of 109P1 D4 expression in the patient, the extent of circulating shed 109P1D4 antigen, the desired steady-state concentration level, frequency of treatment, and the influence of chemotherapeutic or other agents used in combination with the treatment method of the invention, as well as the health status of a particular patient. Non-limiting preferred human unit doses are, for example, 500ug-1 mg, 1 mg - 50mg, 50mg-100mg, 100mg-200mg, 200mg-300mg, 400mg-500mg, 500mg-600mg, 600mg-700mg, 700mg- 800mg, 800mg-900mg, 900mg-1g, or 1 mg-700mg. In certain embodiments, the dose is in a range of 2-5 mg/kg body weight, e. g., with follow on weekly doses of 1-3 mg/kg ; 0. 5mg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 1 Omg/kg body weight followed, e. g., in two, three or four weeks by weekly doses ; 0. 5-10mg/kg body weight, e. g., followed in two, three or four weeks by weekly doses ; 225, 250, 275, 300, 325, 350, 375, 400mg ma of body area weekly ; 1-600mg m2 of body area weekly ; 225-400mg m2 of body area weekly ; these does can be followed by weekly doses for 2, 3, 4, 5, 6, 7, 8, 9, 19, 11, 12 or more weeks.

In one embodiment, human unit dose forms of polynucleotides comprise a suitable dosage range or effective amount that provides any therapeutic effect. As appreciated by one of ordinary skill in the art a therapeutic effect depends on a number of factors, including the sequence of the polynucleotide, molecular weight of the polynucleotide and route of administration. Dosages are generally selected by the physician or other health care professional in accordance with a variety of parameters known in the art, such as severity of symptoms, history of the patient and the like. Generally, for a polynucleotide of about 20 bases, a dosage range may be selected from, for example, an independently selected lower limit such as about 0. 1, 0. 25, 0. 5, 1, 2, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 300, 400 or 500 mg/kg up to an independently selected upper limit, greater than the lower limit, of about 60, 80, 100, 200, 300, 400, 500, 750, 1000, 1500, 2000, 3000, 4000, 5000, 6000, 7000, 8000, 9000 or 10, 000 mg/kg. For example, a dose may be about any of the following : 0. 1 to 100 mg/kg, 0. 1 to 50 mg/kg, 0. 1 to 25 mg/kg, 0. 1 to 10 mg/kg, 1 to 500 mg/kg, 100 to 400 mg/kg, 200 to 300 mg/kg, 1 to 100 mg/kg, 100 to 200 mg/kg, 300 to 400 mg/kg, 400 to 500 mg/kg, 500 to 1000 mg/kg, 500 to 5000 mg/kg, or 500 to 10, 000 mg/kg. Generally, parenteral routes of administration may require higher doses of polynucleotide compared to more direct application to the nucleotide to diseased tissue, as do polynucleotides of increasing length.

In one embodiment, human unit dose forms of T-cells comprise a suitable dosage range or effective amount that provides any therapeutic effect. As appreciated by one of ordinary skill in the art, a therapeutic effect depends on a number of factors. Dosages are generally selected by the physician or other health care professional in accordance with a variety of parameters known in the art, such as severity of symptoms, history of the patient and the like. A dose may be about 104 cells to about 106 cells, about 106 cells to about 108 cells, about 108 to about 1011 cells, or about 108 to about 5 x 101"ceins.

A dose may also about 106 cells/m2 to about 1010 celIS/M2, or about 106 cells/m2 to about 108 cells/m2.

Proteins (s) of the invention, and/or nucleic acids encoding the protein (s), can also be administered via liposomes, which may also serve to : 1) target the proteins (s) to a particular tissue, such as lymphoid tissue ; 2) to target selectively to diseases cells ; or, 3) to increase the half-life of the peptide composition. Liposomes include emulsions, foams, micelles, insoluble monolayers, liquid crystals, phospholipid dispersions, lamella layers and the like. In these preparations, the peptide to be delivered is incorporated as part of a liposome, alone or in conjunction with a molecule which binds to a receptor prevalent among lymphoid cells, such as monoclonal antibodies which bind to the CD45 antigen, or with other therapeutic or immunogenic compositions. Thus, liposomes either filled or decorated with a desired peptide of the invention can be directed to the site of lymphoid cells, where the liposomes then deliver the peptide compositions. Liposomes for use in accordance with the invention are formed from standard vesicle-forming lipids, which generally include neutral and negatively charged phospholipids and a sterol, such as cholesterol. The selection of lipids is generally guided by consideration of, e. g., liposome size, acid lability and stability of the liposomes in the blood stream. A variety of methods are available for preparing liposomes, as described in, e. g., Szoka, et al., Ann. Rev. Biophys. Bioeng. 9 : 467 (1980), and U. S.

Patent Nos. 4, 235, 871, 4, 501, 728, 4, 837, 028, and 5, 019, 369.

For targeting cells of the immune system, a ligand to be incorporated into the liposome can include, e. g., antibodies or fragments thereof specific for cell surface determinants of the desired immune system cells. A liposome suspension containing a peptide may be administered intravenously, locally, topically, etc. in a dose which varies according to, inter alia, the manner of administration, the peptide being delivered, and the stage of the disease being treated.

For solid compositions, conventional nontoxic solid carriers may be used which include, for example, pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharin, talcum, cellulose, glucose, sucrose, magnesium carbonate, and the like. For oral administration, a pharmaceutical acceptable nontoxic composition is formed by incorporating any of the normally employed excipients, such as those carriers previously listed, and generally 10- 95% of active ingredient, that is, one or more peptides of the invention, and more preferably at a concentration of 25%-75%.

For aerosol administration, immunogenic peptides are preferably supplied in finely divided form along with a surfactant and propellant. Typical percentages of peptides are about 0. 01%-20% by weight, preferably about 1%-10%. The surfactant must, of course, be nontoxic, and preferably soluble in the propellant. Representative of such agents are the esters or partial esters of fatty acids containing from about 6 to 22 carbon atoms, such as caproic, octanoic, lauric, palmitic, stearic, linoleic, linolenic, olesteric and oleic acids with an aliphatic polyhydric alcohol or its cyclic anhydride. Mixed esters, such as mixed or natural glycerides may be employed. The surfactant may constitute about 0. 1 %-20% by weight of the composition, preferably about 0. 25-5%. The balance of the composition is ordinarily propellant. A carrier can also be included, as desired, as with, e. g., lecithin for intranasal delivery.

XI.) Diagnostic and Prognostic Embodiments of 109P1D4.

As disclosed herein, 109P1 D4 polynucleotides, polypeptides, reactive cytotoxic T cells (CTL), reactive helper T cells (HTL) and anti-polypeptide antibodies are used in well known diagnostic, prognostic and therapeutic assays that examine conditions associated with dysregulated cell growth such as cancer, in particular the cancers listed in Table I (see, e. g., both its specific pattern of tissue expression as well as its overexpression in certain cancers as described for example in the Example entitled"Expression analysis of 109P1 D4 in normal tissues, and patient specimens").

109P1D4 can be analogized to a prostate associated antigen PSA, the archetypal marker that has been used by medical practitioners for years to identify and monitor the presence of prostate cancer (see, e. g., Merrill et a/., J. Urol. 163 (2) : 503-5120 (2000) ; Polascik et al., J. Urol. Aug ; 162 (2) : 293-306 (1999) and Fortier et a/., J. Nat. Cancer lnst. 91 (19) : 1635- 1640 (1999)). A variety of other diagnostic markers are also used in similar contexts including p53 and K-ras (see, e. g., Tulchinsky et al., lnt J Mol Med 1999 Jul 4 (1) : 99-102 and Minimoto et al., Cancer Detect Prev 2000 ; 24 (1) : 1-12). Therefore, this disclosure of 109P1 D4 polynucleotides and polypeptides (as well as 109P1 D4 polynucleotide probes and anti-109P1 D4 antibodies used to identify the presence of these molecules) and their properties allows skilled artisans to utilize these molecules in methods that are analogous to those used, for example, in a variety of diagnostic assays directed to examining conditions associated with cancer.

Typical embodiments of diagnostic methods which utilize the 109P1D4 polynucleotides, polypeptides, reactive T cells and antibodies are analogous to those methods from well-established diagnostic assays, which employ, e. g., PSA polynucleotides, polypeptides, reactive T cells and antibodies. For example, just as PSA polynucleotides are used as probes (for example in Northern analysis, see, e. g., Sharief et aL, Biochem. Mol. Biol. Int. 33 (3) : 567-74 (1994)) and primers (for example in PCR analysis, see, e. g., Okegawa et al., J. Urol. 163 (4) : 1189-1190 (2000)) to observe the presence and/or the level of PSA mRNAs in methods of monitoring PSA overexpression or the metastasis of prostate cancers, the 109P1 D4 polynucleotides described herein can be utilized in the same way to detect 109P1D4 overexpression or the metastasis of prostate and other cancers expressing this gene. Alternatively, just as PSA polypeptides are used to generate antibodies specific for PSA which can then be used to observe the presence and/or the level of PSA proteins in methods to monitor PSA protein overexpression (see, e. g., Stephan et a/., Urology 55 (4) : 560-3 (2000)) or the metastasis of prostate cells (see, e. g., Alanen et al., Pathol. Res. Pract. 192 (3) : 233-7 (1996)), the 109PI D4 polypeptides described herein can be utilized to generate antibodies for use in detecting 109P1 D4 overexpression or the metastasis of prostate cells and cells of other cancers expressing this gene.

Specifically, because metastases involves the movement of cancer cells from an organ of origin (such as the lung or prostate gland etc.) to a different area of the body (such as a lymph node), assays which examine a biological sample for the presence of cells expressing 109P1 D4 polynucleotides and/or polypeptides can be used to provide evidence of metastasis. For example, when a biological sample from tissue that does not normally contain 109P1 D4-expressing cells (lymph node) is found to contain 109P1 D4-expressing cells such as the 109P1D4 expression seen in LAPC4 and LAPC9, xenografts isolated from lymph node and bone metastasis, respectively, this finding is indicative of metastasis.

Alternatively 109P1 D4 polynucleotides and/or polypeptides can be used to provide evidence of cancer, for example, when cells in abiologicalsamplethatdonotnormallyexpress 109P1D40rexpress 109PlD4atadifferentlevel are found to express 109P1D4 or have an increased expression of 109P1D4 (see, e. g., the 109P1D4 expression in the cancers listed in Table I and in patient samples etc. shown in the accompanying Figures). In such assays, artisans may further wish to generate supplementary evidence of metastasis by testing the biological sample for the presence of a second tissue restricted marker (in addition to 109P1D4) such as PSA, PSCA etc. (see, e. g., Alanen et al., Pathol. Res. Pract. 192 (3) : 233- 237 (1996)).

The use of immunohistochemistry to identify the presence of a 109P1D4 polypeptide within a tissue section can indicate an altered state of certain cells within that tissue. It is well understood in the art that the ability of an antibody to localize to a polypeptide that is expressed in cancer cells is a way of diagnosing presence of disease, disease stage, progression and/or tumor aggressiveness. Such an antibody can also detect an altered distribution of the polypeptide within the cancer cells, as compared to corresponding non-malignant tissue.

The 109P1 D4 polypeptide and immunogenic compositions are also useful in view of the phenomena of altered subcellular protein localization in disease states. Alteration of cells from normal to diseased state causes changes in cellular morphology and is often associated with changes in subcellular protein localization/distribution. For example, cell membrane proteins that are expressed in a polarized manner in normal cells can be altered in disease, resulting in distribution of the protein in a non-polar manner over the whole cell surface.

The phenomenon of altered subcellular protein localization in a disease state has been demonstrated with MUC1 and Her2 protein expression by use of immunohistochemical means. Normal epithelial cells have a typical apical distribution of MUC1, in addition to some supranudear localization of the glycoprotein, whereas malignant lesions often demonstrate an apolar staining pattern (Diaz et al, The Breast Journal, 7 ; 40-45 (2001) ; Zhang et a/, Clinical Cancer Research, 4 ; 2669-2676 (1998) : Cao, et al, The Journal of Histochemistry and Cytochemistry, 45 : 1547-1557 (1997)). In addition, normal breast epithelium is either negative for Her2 protein or exhibits only a basolateral distribution whereas malignant cells can express the protein over the whole cell surface (De Potter, et al, International Journal of Cancer, 44 ; 969-974 (1989) : McCormick, et al, 117 ; 935-943 (2002)). Alternatively, distribution of the protein may be altered from a surface only localization to include diffuse cytoplasmic expression in the diseased state. Such an example can be seen with MUC1 (Diaz, et al, The Breast Journal, 7 : 40-45 (2001)).

Alteration in the localization/distribution of a protein in the cell, as detected by immunohistochemical methods, can also provide valuable information concerning the favorability of certain treatment modalities. This last point is illustrated by a situation where a protein may be intracellular in normal tissue, but cell surface in malignant cells ; the cell surface location makes the cells favorably amenable to antibody-based diagnostic and treatment regimens. When such an alteration of protein localization occurs for 109P1D4, the 109PI D4 protein and immune responses related thereto are very useful.

Accordingly, the ability to determine whether alteration of subcellular protein localization occurred for 24P4C12 make the 109PI D4 protein and immune responses related thereto very useful. Use of the 1 O9P1 D4 compositions allows those skilled in the art to make important diagnostic and therapeutic decisions.

Immunohistochemical reagents specific to 109P1D4 are also useful to detect metastases of tumors expressing 109P1D4 when the polypeptide appears in tissues where 109P1D4 is not normally produced.

Thus, 109P1 D4 polypeptides and antibodies resulting from immune responses thereto are useful in a variety of important contexts such as diagnostic, prognostic, preventative and/or therapeutic purposes known to those skilled in the art.

Just as PSA polynucleotide fragments and polynucleotide variants are employed by skilled artisans for use in methods of monitoring PSA, 109P1 D4 polynucleotide fragments and polynucleotide variants are used in an analogous manner, In particular, typical PSA polynucleotides used in methods of monitoring PSA are probes or primers which consist of fragments of the PSA cDNA sequence. Illustrating this, primers used to PCR amplify a PSA polynucleotide must include less than the whole PSA sequence to function in the polymerase chain reaction. In the context of such PCR reactions, skilled artisans generally create a variety of different polynucleotide fragments that can be used as primers in order to amplify different portions of a polynucleotide of interest or to optimize amplification reactions (see, e. g., Caetano-Anolles, G.

Biotechniques 25 (3) : 472-476, 478-480 (1998) ; Robertson etal., Methods Mol. Biol. 98 : 121-154 (1998)). An additional illustration of the use of such fragments is provided in the Example entitled"Expression analysis of 109P1 D4 in normal tissues, and patient specimens,"where a 109P1 D4 polynucleotide fragment is used as a probe to show the expression of 109P1D4 RNAs in cancer cells. In addition, variant polynucleotide sequences are typically used as primers and probes for the corresponding mRNAs in PCR and Northern analyses (see, e. g., Sawai et al., Fetal Diagn. Ther. 1996 Nov-Dec 11 (6) : 407-13 and Current Protocols In Molecular Biology, Volume 2, Unit 2, Frederick M. Ausubel et al. eds., 1995)).

Polynucleotide fragments and variants are useful in this context where they are capable of binding to a target polynucleotide sequence (e. g., a 109P1 D4 polynucleotide shown in Figure 2 or variant thereof) under conditions of high stringency.

Furthermore, PSA polypeptides which contain an epitope that can be recognized by an antibody or T cell that specifically binds to that epitope are used in methods of monitoring PSA. 109P1 D4 polypeptide fragments and polypeptide analogs or variants can also be used in an analogous manner. This practice of using polypeptide fragments or polypeptide variants to generate antibodies (such as anti-PSA antibodies or T cells) is typical in the art with a wide variety of systems such as fusion proteins being used by practitioners (see, e. g., Current Protocols In Molecular Biology, Volume 2, Unit 16, Frederick M. Ausubel et aL eds., 1995). In this context, each epitope (s) functions to provide the architecture with which an antibody or T cell is reactive. Typically, skilled artisans create a variety of different polypeptide fragments that can be used in order to generate immune responses specific for different portions of a polypeptide of interest (see, e. g., U. S. Patent No.

5, 840, 501 and U. S. Patent No. 5, 939, 533). For example it may be preferable to utilize a polypeptide comprising one of the 109P1 D4 biological motifs discussed herein or a motif-bearing subsequence which is readily identified by one of skill in the art based on motifs available in the art PolypepEde fragments, variants or analogs are typically useful in this context as long as they comprise an epitope capable of generating an antibody or T cell specific for a target polypeptide sequence (e. g. a 109P1D4 polypeptide shown in Figure 3).

As shown herein, the 109P1 D4 polynucleotides and polypeptides (as well as the 109P1 D4 polynucleotide probes and anti-109P1 D4 antibodies or T cells used to identify the presence of these molecules) exhibit specific properties that make them useful in diagnosing cancers such as those listed in Table 1. Diagnostic assays that measure the presence of 109P1 D4 gene products, in order to evaluate the presence or onset of a disease condition described herein, such as prostate cancer, are used to identify patients for preventive measures or further monitoring, as has been done so successfully with PSA. Moreover, these materials satisfy a need in the art for molecules having similar or complementary characteristics to PSA in situations where, for example, a definite diagnosis of metastasis of prostatic origin cannot be made on the basis of a test for PSA alone (see, e. g., Alanen et al., Pathol. Res. Pract. 192 (3) : 233-237 (1996)), and consequently, materials such as 1 O9P1 D4 polynucleotides and polypeptides (as well as the 109P1D4 polynucleotide probes and anti- 109P1 D4 antibodies used to identify the presence of these molecules) need to be employed to confirm a metastases of prostatic origin.

Finally, in addition to their use in diagnostic assays, the 109P1 D4 polynucleotides disclosed herein have a number of other utilities such as their use in the identification of oncogenetic associated chromosomal abnormalities in the chromosomal region to which the 109P1D4 gene maps (see the Example entitled"Chromosomal Mapping of 109P1D4" below). Moreover, in addition to their use in diagnostic assays, the 109P1 D4-related proteins and polynucleotides disclosed herein have other utilities such as their use in the forensic analysis of tissues of unknown origin (see, e. g., Takahama K Forensic Sci Int 1996 Jun 28 ; 80 (1-2) : 63-9).

Additionally, 109P1 D4-related proteins or polynucleotides of the invention can be used to treat a pathologic condition characterized by the over-expression of 109P1 D4. For example, the amino acid or nucleic acid sequence of Figure 2 or Figure 3, or fragments of either, can be used to generate an immune response to a 109P1D4 antigen. Antibodies or other molecules that react with 109P1 D4 can be used to modulate the function of this molecule, and thereby provide a therapeutic benefit.

X) !.) inhibition of 109P1 D4 Protein Function The invention includes various methods and compositions for inhibiting the binding of 109P1 D4 to its binding partner or its association with other protein (s) as well as methods for inhibiting 109P1D4 function.

XII. A.) Inhibition of 109P1 D4 With Intracellular Antibodies In one approach, a recombinant vector that encodes single chain antibodies that specifically bind to 109P1 D4 are introduced into 109P1 D4 expressing cells via gene transfer technologies. Accordingly, the encoded single chain anti- 109P1D4 antibody is expressed intracellularly, binds to 109P1D4 protein, and thereby inhibits its function. Methods for engineering such intracellular single chain antibodies are well known. Such intracellular antibodies, also known as "intrabodies", are specifically targeted to a particular compartment within the cell, providing control over where the inhibitory activity of the treatment is focused. This technology has been successfully applied in the art (for review, see Richardson and Marasco, 1995, TIBTECH vol. 13). lntrabodies have been shown to virtually eliminate the expression of otherwise abundant cell surface receptors (see, e. g., Richardson et al., 1995, Proc. Natl. Acad. Sci. USA 92 : 3137-3141 ; Beerli etal., 1994, J.

Biol. Chem. 289 : 23931-23936 ; Deshane et al., 1994, Gene Ther. 1 : 332-337).

Single chain antibodies comprise the variable domains of the heavy and light chain joined by a flexible linker polypeptide, and are expressed as a single polypeptide. Optionally, single chain antibodies are expressed as a single chain variable region fragment joined to the light chain constant region. Well-known intracellular trafficking signals are engineered into recombinant polynucleotide vectors encoding such single chain antibodies in order to target precisely the intrabody to the desired intracellular compartment. For example, intrabodies targeted to the endoplasmic reticulum (ER) are engineered to incorporate a leader peptide and, optionally, a C-terminal ER retention signal, such as the KDEL amino acid motif.

Intrabodies intended to exert activity in the nucleus are engineered to include a nuclear localization signal. Lipid moieties are joined to intrabodies in order to tether the intrabody to the cytosolic side of the plasma membrane. Intrabodies can also be targeted to exert function in the cytosol. For example, cytosolic intrabodies are used to sequester factors within the cytosol, thereby preventing them from being transported to their natural cellular destination. in one embodiment, intrabodies are used to capture 109P1D4 in the nucleus, thereby preventing its activity within the nucleus. Nuclear targeting signals are engineered into such 109P1 D4 intrabodies in order to achieve the desired targeting. Such 109P1D4 intrabodies are designed to bind specifically to a particular 109P1D4 domain. In another embodiment, cytosolic intrabodies that specifically bind to a 109P1D4 protein are used to prevent 109P1D4 from gaining access to the nucleus, thereby preventing it from exerting any biological activity within the nucleus (e. g., preventing 109P1 D4 from forming transcription complexes with other factors).

In order to specifically direct the expression of such intrabodies to particular cells, the transcription of the intrabody is placed under the regulatory control of an appropriate tumor-specific promoter and/or enhancer. In order to target intrabody expression specifically to prostate, for example, the PSA promoter and/or promoter/enhancer can be utilized (See, for example, U. S. Patent No. 5, 919, 652 issued 6 July 1999).

XII. B.) Inhibition of 109P1 D4 with Recombinant Proteins In another approach, recombinant molecules bind to 109P1D4 and thereby inhibit 109P1D4 function. For example, these recombinant molecules prevent or inhibit 109P1D4 from accessing/binding to its binding partner (s) or associating with other protein (s). Such recombinant molecules can, for example, contain the reactive part (s) of a 109P1 D4 specific antibody molecule. in a particular embodiment, the 109P1 D4 binding domain of a 109P1 D4 binding partner is engineered into a dimeric fusion protein, whereby the fusion protein comprises two 1 09P1D4 ligand binding domains linked to the Fc portion of a human IgG, such as human IgG1. Such gG portion can contain, for example, the CH2 and CH3 domains and the hinge region, but not the CH1 domain. Such dimeric fusion proteins are administered in soluble form to patients suffering from a cancer associated with the expression of 109P1 D4, whereby the dimeric fusion protein specifically binds to 109P1 D4 and blocks 109P1 D4 interaction with a binding partner. Such dimeric fusion proteins are further combined into multimeric proteins using known antibody linking technologies.

XII. C.) Inhibition of 109P1D4Transcription orTranslation The present invention also comprises various methods and compositions for inhibiting the transcription of the 109P1D4 gene. Similarly, the invention also provides methods and compositions for inhibiting the translation of 109P1 D4 mRNA into protein.

In one approach, a method of inhibiting the transcription of the 109P1 D4 gene comprises contacting the 109P1 D4 gene with a 109P1 D4 antisense polynucleotide. In another approach, a method of inhibiting 109P1 D4 mRNA translation comprises contacting a 109P1 D4 mRNA with an antisense polynucleotide. In another approach, a 109P1 D4 specific ribozyme is used to cleave a 109P1 D4 message, thereby inhibiting translation. Such antisense and ribozyme based methods can also be directed to the regulatory regions of the 109P1 D4 gene, such as 109P1 D4 promoter and/or enhancer elements. Similarly, proteins capable of inhibiting a 109P1 D4 gene transcription factor are used to inhibit 109P1 D4 mRNA transcription. The various polynucleotides and compositions useful in the aforementioned methods have been described above. The use of antisense and ribozyme molecules to inhibit transcription and translation is well known in the art.

Other factors that inhibit the transcription of 109P1 D4 by interfering with 109P1 D4 transcriptional activation are also useful to treat cancers expressing 109P1D4. Similarly, factors that interfere with 109P1D4 processing are useful to treat cancers that express 109PI D4. Cancer treatment methods utilizing such factors are also within the scope of the invention SII. D.) General Considerations for Therapeutic Strategies Gene transfer and gene therapy technologies can be used to deliver therapeutic polynucleotide molecules to tumor cells synthesizing 109P1D4 (i. e., antisense, ribozyme, polynucleotides encoding intrabodies and other 109P1D4 inhibitory molecules).

A number of gene therapy approaches are known in the art. Recombinant vectors encoding 109P1 D4 antisense polynucleotides, ribozymes, factors capable of interfering with 109P1 D4 transcription, and so forth, can be delivered to target tumor cells using such gene therapy approaches.

The above therapeutic approaches can be combined with any one of a wide variety of surgical, chemotherapy or radiation therapy regimens. The therapeutic approaches of the invention can enable the use of reduced dosages of chemotherapy (or other therapies) and/or less frequent administration, an advantage for all patients and particularly for those that do not tolerate the toxicity of the chemotherapeutic agent well.

The anti-tumor activity of a particular composition (e. g., antisense, ribozyme, intrabody), or a combination of such compositions, can be evaluated using various in vitro and in vivo assay systems. In vitro assays that evaluate therapeutic activity include cell growth assays, soft agar assays and other assays indicative of tumor promoting activity, binding assays capable of determining the extent to which a therapeutic composition will inhibit the binding of 109P1 D4 to a binding partner, etc.

In vivo, the effect of a 109P1 D4 therapeutic composition can be evaluated in a suitable animal model. For example, xenogenic prostate cancer models can be used, wherein human prostate cancer explants or passaged xenograft tissues are introduced into immune compromised animals, such as nude or SCID mice (Klein et al., 1997, Nature Medicine 3 : 402-408). For example, PCT Patent Application W098/16628 and U. S. Patent 6, 107, 540 describe various xenograft models of human prostate cancer capable of recapitulating the development of primary tumors, micrometastasis, and the formation of osteoblastic metastases characteristic of late stage disease. Efficacy can be predicted using assays that measure inhibition of tumor formation, tumor regression or metastasis, and the like.

In vivo assays that evaluate the promotion of apoptosis are useful in evaluating therapeutic compositions. In one embodiment, xenografts from tumor bearing mice treated with the therapeutic composition can be examined for the presence of apoptotic foci and compared to untreated control xenograft-bearing mice. The extent to which apoptotic foci are found in the tumors of the treated mice provides an indication of the therapeutic efficacy of the composition.

The therapeutic compositions used in the practice of the foregoing methods can be formulated into pharmaceutical compositions comprising a carrier suitable for the desired delivery method. Suitable carriers include any material that when combined with the therapeutic composition retains the anti-tumor function of the therapeutic composition and is generally non-reactive with the patient's immune system. Examples include, but are not limited to, any of a number of standard pharmaceutical carriers such as sterile phosphate buffered saline solutions, bacteriostatic water, and the like (see, generally, Remington's Pharmaceutical Sciences 16i Edition, A. Osal., Ed., 1980).

Therapeutic formulations can be solubilized and administered via any route capable of delivering the therapeutic composition to the tumor site. Potentially effective routes of administration include, but are not limited to, intravenous, parenteral, intraperitoneal, intramuscular, intratumor, intradermal, intraorgan, orthotopic, and the like. A preferred formulation for intravenous injection comprises the therapeutic composition in a solution of preserved bacteriostatic water, sterile unpreserved water, and/or diluted in polyvinylchloride or polyethylene bags containing 0. 9% sterile Sodium Chloride for Injection, USP. Therapeutic protein preparations can be lyophilized and stored as sterile powders, preferably under vacuum, and then reconstituted in bacteriostatic water (containing for example, benzyl alcohol preservative) or in sterile water prior to injection.

Dosages and administration protocols for the treatment of cancers using the foregoing methods will vary with the method and the target cancer, and will generally depend on a number of other factors appreciated in the art.

XIII.) Identification. Characterization and Use of Modulators of 109P1D4 Methods to identify and Use Modulators In one embodiment, screening is performed to identify modulators that induce or suppress a particular expression profile, suppress or induce specific pathways, preferably generating the associated phenotype thereby. In another embodiment, having identified differentially expressed genes important in a particular state ; screens are performed to identify modulators that alter expression of individual genes, either increase or decrease. In another embodiment, screening is performed to identify modulators that alter a biological function of the expression product of a differentially expressed gene.

Again, having identified the importance of a gene in a particular state, screens are performed to identify agents that bind and/or modulate the biological activity of the gene product.

In addition, screens are done for genes that are induced in response to a candidate agent. After identifying a modulator (one that suppresses a cancer expression pattern leading to a normal expression pattern, or a modulator of a cancer gene that leads to expression of the gene as in normal tissue) a screen is performed to identify genes that are specifically modulated in response to the agent. Comparing expression profiles between normal tissue and agent-treated cancer tissue reveals genes that are not expressed in normal tissue or cancer tissue, but are expressed in agent treated tissue, and vice versa. These agent-specific sequences are identified and used by methods described herein for cancer genes or proteins, In particular these sequences and the proteins they encode are used in marking or identifying agent- treated cells. In addition, antibodies are raised against the agent-induced proteins and used to target novel therapeutics to the treated cancer tissue sample.

Modulator-related identification and Screening Assays : Gene Expression-related Assays Proteins, nucleic acids, and antibodies of the invention are used in screening assays. The cancer-associated proteins, antibodies, nucleic acids, modified proteins and cells containing these sequences are used in screening assays, such as evaluating the effect of drug candidates on a"gene expression profile,"expression profile of polypeptides or alteration of biological function. In one embodiment, the expression profiles are used, preferably in conjunction with high throughput screening techniques to allow monitoring for expression profile genes after treatment with a candidate agent (e. g., Davis, GF, et al, J Biol Screen 7 : 69 (2002) ; Zlokarnik, et al., Science 279 : 84-8 (1998) ; Heid, Genome Res 6 : 986- 94, 1996).

The cancer proteins, antibodies, nucleic acids, modified proteins and cells containing the native or modified cancer proteins or genes are used in screening assays. That is, the present invention comprises methods for screening for compositions which modulate the cancer phenotype or a physiological function of a cancer protein of the invention. This is done on a gene itself or by evaluating the effect of drug candidates on a"gene expression profile"or biological function. In one embodiment, expression profiles are used, preferably in conjunction with high throughput screening techniques to allow monitoring after treatment with a candidate agent, see Zlokamik, supra.

A variety of assays are executed directed to the genes and proteins of the invention. Assays are run on an individual nucleic acid or protein level. That is, having identified a particular gene as up regulated in cancer, test compounds are screened for the ability to modulate gene expression or for binding to the cancer protein of the invention."Modulation"in this context includes an increase or a decrease in gene expression. The preferred amount of modulation will depend on the original change of the gene expression in normal versus tissue undergoing cancer, with changes of at least 10%, preferably 50%, more preferably 100-300%, and in some embodiments 300-1000% or greater. Thus, if a gene exhibits a 4-fold increase in cancer tissue compared to normal tissue, a decrease of about four-fold is often desired ; similarly, a 10-fold decrease in cancer tissue compared to normal tissue a target value of a 10-fold increase in expression by the test compound is often desired. Modulators that exacerbate the type of gene expression seen in cancer are also useful, e. g., as an upregulated target in further analyses.

The amount of gene expression is monitored using nucleic acid probes and the quantification of gene expression levels, or, alternatively, a gene product itself is monitored, e. g., through the use of antibodies to the cancer protein and standard immunoassays. Proteomics and separation techniques also allow for quantification of expression.

Expression Monitoring to Identify Compounds that Modify Gene Expression In one embodiment, gene expression monitoring, i. e., an expression profile, is monitored simultaneously for a number of entities. Such profiles will typically involve one or more of the genes of Figure 2. In this embodiment, e. g., cancer nucleic acid probes are attached to biochips to detect and quantify cancer sequences in a particular cell. Alternatively, PCR can be used. Thus, a series, e. g., wells of a microtiter plate, can be used with dispensed primers in desired wells. A PCR reaction can then be performed and analyzed for each well.

Expression monitoring is performed to identify compounds that modify the expression of one or more cancer- associated sequences, e. g., a polynucleotide sequence set out in Figure 2. Generally, a test modulator is added to the cells prior to analysis. Moreover, screens are also provided to identify agents that modulate cancer, modulate cancer proteins of the invention, bind to a cancer protein of the invention, or interfere with the binding of a cancer protein of the invention and an antibody or other binding partner.

In one embodiment, high throughput screening methods involve providing a library containing a large number of potential therapeutic compounds (candidate compounds). Such"combinatorial chemical libraries"are then screened in one or more assays to identify those library members (particular chemical species or subclasses) that display a desired characteristic activity. The compounds thus identified can serve as conventional"lead compounds,"as compounds for screening, or as therapeutics.

In certain embodiments, combinatorial libraries of potential modulators are screened for an ability to bind to a cancer polypeptide or to modulate activity. Conventionally, new chemical entities with useful properties are generated by identifying a chemical compound (called a"lead compound") with some desirable property or activity, e. g., inhibiting activity, creating variants of the lead compound, and evaluating the property and activity of those variant compounds. Often, high throughput screening (HTS) methods are employed for such an analysis.

As noted above, gene expression monitoring is conveniently used to test candidate modulators (e. g., protein, nucleic acid or small molecule). After the candidate agent has been added and the cells allowed to incubate for a period, the sample containing a target sequence to be analyzed is, e. g., added to a biochip.

If required, the target sequence is prepared using known techniques. For example, a sample is treated to lyse the cells, using known lysis buffers, electroporation, etc., with purification and/or amplification such as PCR performed as appropriate. For example, an in vitro transcription with labels covalently attached to the nucleotides is performed. Generally, the nucleic acids are labeled with biotin-FITC or PE, or with cy3 or cy5.

The target sequence can be labeled with, e. g., a fluorescent, a chemiluminescent, a chemical, or a radioactive signal, to provide a means of detecting the target sequence's specific binding to a probe. The label also can be an enzyme, such as alkaline phosphatase or horseradish peroxidase, which when provided with an appropriate substrate produces a product that is detected. Alternatively, the label is a labeled compound or small molecule, such as an enzyme inhibitor, that binds but is not catalyzed or altered by the enzyme. The label also can be a moiety or compound, such as, an epitope tag or biotin which specifically binds to streptavidin. For the example of biotin, the streptavidin is labeled as described above, thereby, providing a detectable signal for the bound target sequence. Unbound labeled streptavidin is typically removed prior to analysis.

As will be appreciated by those in the art, these assays can be direct hybridization assays or can comprise "sandwich assays", which include the use of multiple probes, as is generally outlined in U. S. Patent Nos. 5, 681, 702 ; 5, 597, 909 ; 5, 545, 730 ; 5, 594, 117 ; 5, 591, 584 ; 5, 571, 670 ; 5, 580, 731 ; 5, 571, 670 ; 5, 591, 584 ; 5, 624, 802 ; 5, 635, 352 ; 5, 594, 118 ; 5, 359, 100 ; 5, 124, 246 ; and 5, 681, 697. In this embodiment, in general, the target nucleic acid is prepared as outlined above, and then added to the biochip comprising a plurality of nucleic acid probes, under conditions that allow the formation of a hybridization complex.

A variety of hybridization conditions are used in the present invention, including high, moderate and low stringency conditions as outlined above. The assays are generally run under stringency conditions which allow formation of the label probe hybridization complex only in the presence of target. Stringency can be controlled by altering a step parameter that is a thermodynamic variable, including, but not limited to, temperature, formamide concentration, salt concentration, chaotropic salt concentration pH, organic solvent concentration, etc. These parameters may also be used to control non-specific binding, as is generally outlined in U. S. Patent No. 5, 681, 697. Thus, it can be desirable to perform certain steps at higher stringency conditions to reduce non-specific binding.

The reactions outlined herein can be accomplished in a variety of ways. Components of the reaction can be added simultaneously, or sequentially, in different orders, with preferred embodiments outlined below. In addition, the reaction may include a variety of other reagents. These include salts, buffers, neutral proteins, e. g. albumin, detergents, etc. which can be used to facilitate optimal hybridization and detection, and/or reduce nonspecific or background interactions. Reagents that otherwise improve the efficiency of the assay, such as protease inhibitors, nuclease inhibitors, anti-microbial agents, etc., may also be used as appropriate, depending on the sample preparation methods and purity of the target. The assay data are analyzed to determine the expression levels of individual genes, and changes in expression levels as between states, forming a gene expression profile.

Biological Activity-related Assays The invention provides methods identify or screen for a compound that modulates the activity of a cancer-related gene or protein of the invention. The methods comprise adding a test compound, as defined above, to a cell comprising a cancer protein of the invention. The cells contain a recombinant nucleic acid that encodes a cancer protein of the invention.

In another embodiment, a library of candidate agents is tested on a plurality of cells.

In one aspect, the assays are evaluated in the presence or absence or previous or subsequent exposure of physiological signals, e. g. hormones, antibodies, peptides, antigens, cytokines, growth factors, action potentials, pharmacological agents including chemotherapeutics, radiation, carcinogenics, or other cells (i. e., cell-cell contacts). In another example, the determinations are made at different stages of the cell cycle process. In this way, compounds that modulate genes or proteins of the invention are identified. Compounds with pharmacological activity are able to enhance or interfere with the activity of the cancer protein of the invention. Once identified, similar structures are evaluated to identify critical structural features of the compound.

In one embodiment, a method of modulating (e. g., inhibiting) cancer cell division is provided ; the method comprises administration of a cancer modulator. In another embodiment, a method of modulating (e. g., inhibiting) cancer is provided ; the method comprises administration of a cancer modulator. In a further embodiment, methods of treating cells or individuals with cancer are provided ; the method comprises administration of a cancer modulator.

In one embodiment, a method for modulating the status of a cell that expresses a gene of the invention is provided.

As used herein status comprises such art-accepted parameters such as growth, proliferation, survival, function, apoptosis, senescence, location, enzymatic activity, signal transduction, etc. of a cell. In one embodiment, a cancer inhibitor is an antibody as discussed above. In another embodiment, the cancer inhibitor is an antisense molecule. A variety of cell growth, proliferation, and metastasis assays are known to those of skill in the art, as described herein.

High Throughput Screening to Identify Modulators The assays to identify suitable modulators are amenable to high throughput screening. Preferred assays thus detect enhancement or inhibition of cancer gene transcription, inhibition or enhancement of polypeptide expression, and inhibition or enhancement of polypeptide activity.

In one embodiment, modulators evaluated in high throughput screening methods are proteins, often naturally occurring proteins or fragments of naturally occurring proteins. Thus, e. g., cellular extracts containing proteins, or random or directed digests of proteinaceous cellular extracts, are used. In this way, libraries of proteins are made for screening in the methods of the invention. Particularly preferred in this embodiment are libraries of bacterial, fungal, viral, and mammalian proteins, with the latter being preferred, and human proteins being especially preferred. Particularly useful test compound will be directed to the class of proteins to which the target belongs, e. g., substrates for enzymes, or ligands and receptors.

Use of Soft Agar Growth and Colony Formation to identify and Characterize Modulators Normal cells require a solid substrate to attach and grow. When cells are transformed, they lose this phenotype and grow detached from the substrate. For example, transformed cells can grow in stirred suspension culture or suspended in semi-solid media, such as semi-solid or soft agar. The transformed cells, when transfected with tumor suppressor genes, can regenerate normal phenotype and once again require a solid substrate to attach to and grow. Soft agar growth or colony formation in assays are used to identify modulators of cancer sequences, which when expressed in host cells, inhibit abnormal cellular proliferation and transformation. A modulator reduces or eliminates the host cells'ability to grow suspended in solid or semisolid media, such as agar.

Techniques for soft agar growth or colony formation in suspension assays are described in Freshney, Culture of Animal Cells a Manual of Basic Technique (3rd ed., 1994). See also, the methods section of Garkavtsev et al. (1996), supra.

Evaluation of Contact Inhibition and Growth Density Limitation to Identify and Characterize Modulators Normal cells typically grow in a flat and organized pattern in cell culture until they touch other cells. When the cells touch one another, they are contact inhibited and stop growing. Transformed cells, however, are not contact inhibited and continue to grow to high densities in disorganized foci. Thus, transformed cells grow to a higher saturation density than corresponding normal cells. This is detected morphologically by the formation of a disoriented monolayer of cells or cells in foci. Alternatively, labeling index with (3H)-thymidine at saturation density is used to measure density limitation of growth, similarly an MTT or Alamar blue assay will reveal proliferation capacity of cells and the the ability of modulators to affect same. See Freshney (1994), supra. Transformed cells, when transfected with tumor suppressor genes, can regenerate a normal phenotype and become contact inhibited and would grow to a lower density.

In this assay, labeling index with 3H)-thymidine at saturation density is a preferred method of measuring density limitation of growth. Transformed host cells are transfected with a cancer-associated sequence and are grown for 24 hours at saturation density in non-limiting medium conditions. The percentage of cells labeling with (3H)-thymidine is determined by incorporated cpm.

Contact independent growth is used to identify modulators of cancer sequences, which had led to abnormal cellular proliferation and transformation. A modulator reduces or eliminates contact independent growth, and returns the cells to a normal phenotype.

Evaluation of Growth Factor or Serum Dependence to identify and Characterize Modulators Transformed cells have lower serum dependence than their normal counterparts (see, e. g., Temin, J. Natl. Cancer Inst. 37 : 167-175 (1966) ; Eagle et al., J. Exp. Med 131 : 836-879 (1970)) ; Freshney, supra. This is in part due to release of various growth factors by the transformed cells. The degree of growth factor or serum dependence of transformed host cells can be compared with that of control. For example, growth factor or serum dependence of a cell is monitored in methods to identify and characterize compounds that modulate cancer-associated sequences of the invention.

Use of Tumor-specific Marker Levels to identify and Characterize Modulators Tumor cells release an increased amount of certain factors (hereinafter"tumor specific markers") than their normal counterparts. For example, plasminogen activator (PA) is released from human glioma at a higher level than from normal brain cells (see, e. g., Gullino, Angiogenesis, Tumor Vascularization, and Potential interference with Tumor Growth, in Biological Responses in Cancer, pp. 178-184 (Mihich (ed.) 1985)). Similarly, Tumor Angiogenesis Factor (TAF) is released at a higher level in tumor cells than their normal counterparts. See, e. g., Folkman, Angiogenesis and Cancer, Sem Cancer Biol. (1992)), while bFGF is released from endothelial tumors (Ensoli, B et al).

Various techniques which measure the release of these factors are described in Freshney (1994), supra. Also, see, Unkless et al., J. Biol. Chem. 249 : 4295-4305 (1974) ; Strickland & Beers, J. Biol. Chem. 251 : 5694-5702 (1976) ; Whur et al., Br. J. Cancer 42 : 305 312 (1980) ; Gullino, Angiogenesis, Tumor Vascularization, and Potential Interference with Tumor Growth, in Biological Responses in Cancer, pp. 178-184 (Mihich (ed.) 1985) ; Freshney, Anticancer Res. 5 : 111-130 (1985).

For example, tumor specific marker levels are monitored in methods to identify and characterize compounds that modulate cancer-associated sequences of the invention.

Invasiveness into Matrigel to Identify and Characterize Modulators The degree of invasiveness into Matrigel or an extracellular matrix constituent can be used as an assay to identify and characterize compounds that modulate cancer associated sequences. Tumor cells exhibit a positive correlation between malignancy and invasiveness of cells into Matrigel or some other extracellular matrix constituent. In this assay, tumorigenic cells are typically used as host cells. Expression of a tumor suppressor gene in these host cells would decrease invasiveness of the host cells. Techniques described in Cancer Res. 1999 ; 59 : 6010 ; Freshney (1994), supra, can be used.

Briefly, the level of invasion of host cells is measured by using filters coated with Matrigel or some other extracellular matrix constituent. Penetration into the gel, or through to the distal side of the filter, is rated as invasiveness, and rated histologically by number of cells and distance moved, or by prelabeling the cells with 1251 and counting the radioactivity on the distal side of the filter or bottom of the dish. See, e. g., Freshney (1984), supra.

Evaluation of Tumor Growth In Vivo to identify and Characterize Modulators Effects of cancer-associated sequences on cell growth are tested in transgenic or immune-suppressed organisms.

Transgenic organisms are prepared in a variety of art-accepted ways. For example, knock-out transgenic organisms, e. g., mammals such as mice, are made, in which a cancer gene is disrupted or in which a cancer gene is inserted. Knock-out transgenic mice are made by insertion of a marker gene or other heterologous gene into the endogenous cancer gene site in the mouse genome via homologous recombination. Such mice can also be made by substituting the endogenous cancer gene with a mutated version of the cancer gene, or by mutating the endogenous cancer gene, e. g., by exposure to carcinogens.

To prepare transgenic chimeric animals, e. g., mice, a DNA construct is introduced into the nuclei of embryonic stem cells. Cells containing the newly engineered genetic lesion are injected into a host mouse embryo, which is re- implanted into a recipient female. Some of these embryos develop into chimeric mice that possess germ cells some of which are derived from the mutant cell line. Therefore, by breeding the chimeric mice it is possible to obtain a new line of mice containing the introduced genetic lesion (see, e. g., Capecchi et al., Science 244 : 1288 (1989)). Chimeric mice can be derived according to US Patent 6, 365, 797, issued 2 April 2002 ; US Patent 6, 107, 540 issued 22 August 2000 ; Hogan et al., Manipulating the Mouse Embryo : A laboratory Manual, Cold Spring Harbor Laboratory (1988) and Teratocarcinomas and Embryonic Stem Cells : A Practical Approach, Robertson, ed., IRL Press, Washington, D. C., (1987).

Alternatively, various immune-suppressed or immune-deficient host animals can be used. For example, a genetically athymic"nude"mouse (see, e. g., Giovanella et al., J. Natl. Cancer Inst. 52 : 921 (1974)), a SCID mouse, a thymectornized mouse, or an irradiated mouse (see, e. g., Bradley et al., Br. J. Cancer 38 : 263 (1978) ; Selby et al., Br. J.

Cancer 41 : 52 (1980)) can be used as a host. Transplantable tumor cells (typically about 106 cells) injected into isogenic hosts produce invasive tumors in a high proportion of cases, while normal cells of similar origin will not. In hosts which developed invasive tumors, cells expressing cancer-associated sequences are injected subcutaneously or orthotopically.

Mice are then separated into groups, including control groups and treated experimental groups) e. g. treated with a modulator). After a suitable length of time, preferably 4-8 weeks, tumor growth is measured (e. g., by volume or by its two largest dimensions, or weight) and compared to the control. Tumors that have statistically significant reduction (using, e. g., Student's T test) are said to have inhibited growth.

In Vitro Assays to Identify and Characterize Modulators Assays to identify compounds with modulating activity can be performed in vitro. For example, a cancer polypeptide is first contacted with a potential modulator and incubated for a suitable amount of time, e. g., from 0. 5 to 48 hours. In one embodiment, the cancer polypeptide levels are determined in vitro by measuring the level of protein or mRNA.

The level of protein is measured using immunoassays such as Western blotting, ELISA and the like with an antibody that selectively binds to the cancer polypeptide or a fragment thereof. For measurement of mRNA, amplification, e. g., using PCR, LCR, or hybridization assays, e. g., Northern hybridization, RNAse protection, dot blotting, are preferred. The level of protein or mRNA is detected using directly or indirectly labeled detection agents, e. g., fluorescently or radioactively labeled nucleic acids, radioactively or enzymatically labeled antibodies, and the like, as described herein.

Alternatively, a reporter gene system can be devised using a cancer protein promoter operably linked to a reporter gene such as luciferase, green fluorescent protein, CAT, or P-gal. The reporter construct is typically transfected into a cell.

After treatment with a potential modulator, the amount of reporter gene transcription, translation, or activity is measured according to standard techniques known to those of skill in the art (Davis GF, supra ; Gonzalez, J. & Negulescu, P. Curr.

Opin. Biotechnol. 1998 : 9 : 624).

As outlined above, in vitro screens are done on individual genes and gene products. That is, having identified a particular differentially expressed gene as important in a particular state, screening of modulators of the expression of the gene or the gene product itself is performed.

In one embodiment, screening for modulators of expression of specific gene (s) is performed. Typically, the expression of only one or a few genes is evaluated. In another embodiment, screens are designed to first find compounds that bind to differentially expressed proteins. These compounds are then evaluated for the ability to modulate differentially expressed activity. Moreover, once initial candidate compounds are identified, variants can be further screened to better evaluate structure activity relationships.

Binding Assays to Identify and Characterize Modulators In binding assays in accordance with the invention, a purified or isolated gene product of the invention is generally used. For example, antibodies are generated to a protein of the invention, and immunoassays are run to determine the amount and/or location of protein. Alternatively, cells comprising the cancer proteins are used in the assays.

Thus, the methods comprise combining a cancer protein of the invention and a candidate compound such as a ligand, and determining the binding of the compound to the cancer protein of the invention. Preferred embodiments utilize the human cancer protein ; animal models of human disease of can also be developed and used. Also, other analogous mammalian proteins also can be used as appreciated by those of skill in the art. Moreover, in some embodiments variant or derivative cancer proteins are used.

Generally, the cancer protein of the invention, or the ligand, is non-diffusibly bound to an insoluble support. The support can, e. g., be one having isolated sample receiving areas (a microtiter plate, an array, etc.). The insoluble supports can be made of any composition to which the compositions can be bound, is readily separated from soluble material, and is otherwise compatible with the overall method of screening. The surface of such supports can be solid or porous and of any convenient shape.

Examples of suitable insoluble supports include microtiter plates, arrays, membranes and beads. These are typically made of glass, plastic (e. g., polystyrene), polysaccharide, nylon, nitrocellulose, or Teflon, etc. Microtiter plates and arrays are especially convenient because a large number of assays can be carried out simultaneously, using small amounts of reagents and samples. The particular manner of binding of the composition to the support is not crucial so long as it is compatible with the reagents and overall methods of the invention, maintains the activity of the composition and is nondiffusabie. Preferred methods of binding include the use of antibodies which do not sterically block either the ligand binding site or activation sequence when attaching the protein to the support, direct binding to"sticky"or ionic supports, chemical crosslinking, the synthesis of the protein or agent on the surface, etc. Following binding of the protein or ligand/binding agent to the support, excess unbound material is removed by washing. The sample receiving areas may then be blocked through incubation with bovine serum albumin (BSA), casein or other innocuous protein or other moiety.

Once a cancer protein of the invention is bound to the support, and a test compound is added to the assay.

Alternatively, the candidate binding agent is bound to the support and the cancer protein of the invention is then added.

Binding agents include specific antibodies, non-natural binding agents identified in screens of chemical libraries, peptide analogs, etc.

Of particular interest are assays to identify agents that have a low toxicity for human cells. A wide variety of assays can be used for this purpose, including proliferation assays, cAMP assays, labeled in vitro protein-protein binding assays, electrophoretic mobility shift assays, immunoassays for protein binding, functional assays (phosphorylation assays, etc.) and the like.

A determination of binding of the test compound (ligand, binding agent, modulator, etc.) to a cancer protein of the invention can be done in a number of ways. The test compound can be labeled, and binding determined directly, e. g., by attaching all or a portion of the cancer protein of the invention to a solid support, adding a labeled candidate compound (e. g., a fluorescent label), washing off excess reagent, and determining whether the label is present on the solid support. Various blocking and washing steps can be utilized as appropriate.

In certain embodiments, only one of the components is labeled, e. g., a protein of the invention or ligands labeled.

Alternatively, more than one component is labeled with different labels, e. g., 1125, for the proteins and a fluorophor for the compound. Proximity reagents, e. g., quenching or energy transfer reagents are also useful.

Competitive Binding to Identify and Characterize Modulators In one embodiment, the binding of the"test compound"is determined by competitive binding assay with a "competitor."The competitor is a binding moiety that binds to the target molecule (e. g., a cancer protein of the invention).

Competitors include compounds such as antibodies, peptides, binding partners, ligands, etc. Under certain circumstances, the competitive binding between the test compound and the competitor displaces the test compound. In one embodiment, the test compound is labeled. Either the test compound, the competitor, or both, is added to the protein for a time sufficient to allow binding. Incubations are performed at a temperature that facilitates optimal activity, typically between four and 40°C.

Incubation periods are typically optimized, e. g., to facilitate rapid high throughput screening ; typically between zero and one hour will be sufficient. Excess reagent is generally removed or washed away. The second component is then added, and the presence or absence of the labeled component is followed, to indicate binding.

In one embodiment, the competitor is added first, followed by the test compound. Displacement of the competitor is an indication that the test compound is binding to the cancer protein and thus is capable of binding to, and potentially modulating, the activity of the cancer protein. In this embodiment, either component can be labeled. Thus, e. g., if the competitor is labeled, the presence of label in the post-test compound wash solution indicates displacement by the test compound. Alternatively, if the test compound is labeled, the presence of the label on the support indicates displacement.

In an alternative embodiment, the test compound is added first, with incubation and washing, followed by the competitor. The absence of binding by the competitor indicates that the test compound binds to the cancer protein with higher affinity than the competitor. Thus, if the test compound is labeled, the presence of the label on the support, coupled with a lack of competitor binding, indicates that the test compound binds to and thus potentially modulates the cancer protein of the invention.

Accordingly, the competitive binding methods comprise differential screening to identity agents that are capable of modulating the activity of the cancer proteins of the invention. In this embodiment, the methods comprise combining a cancer protein and a competitor in a first sample. A second sample comprises a test compound, the cancer protein, and a competitor. The binding of the competitor is determined for both samples, and a change, or difference in binding between the two samples indicates the presence of an agent capable of binding to the cancer protein and potentially modulating its activity. That is, if the binding of the competitor is different in the second sample relative to the first sample, the agent is capable of binding to the cancer protein.

Alternatively, differential screening is used to identify drug candidates that bind to the native cancer protein, but cannot bind to modified cancer proteins. For example the structure of the cancer protein is modeled and used in rational drug design to synthesize agents that interact with that site, agents which generally do not bind to site-modified proteins.

Moreover, such drug candidates that affect the activity of a native cancer protein are also identified by screening drugs for the ability to either enhance or reduce the activity of such proteins.

Positive controls and negative controls can be used in the assays. Preferably control and test samples are performed in at least triplicate to obtain statistically significant results. Incubation of all samples occurs for a time sufficient to allow for the binding of the agent to the protein. Following incubation, samples are washed free of non-specifically bound material and the amount of bound, generally labeled agent determined. For example, where a radiolabel is employed, the samples can be counted in a scintillation counter to determine the amount of bound compound.

A variety of other reagents can be included in the screening assays. These include reagents like salts, neutral proteins, e. g. albumin, detergents, etc. which are used to facilitate optimal protein-protein binding and/or reduce non-specific or background interactions. Also reagents that otherwise improve the efficiency of the assay, such as protease inhibitors, nuclease inhibitors, anti-microbial agents, etc., can be used. The mixture of components is added in an order that provides for the requisite binding.

Use of Polvnucleotides to Down-regulate or Inhibit a Protein of the invention.

Polynucleotide modulators of cancer can be introduced into a cell containing the target nucleotide sequence by formation of a conjugate with a ligand-binding molecule, as described in WO 91/04753. Suitable ligand-binding molecules include, but are not limited to, cell surface receptors, growth factors, other cytokines, or other ligands that bind to cell surface receptors. Preferably, conjugation of the ligand binding molecule does not substantially interfere with the ability of the ligand binding molecule to bind to its corresponding molecule or receptor, or block entry of the sense or antisense oligonucleotide or its conjugated version into the cell. Alternatively, a polynucleotide modulator of cancer can be introduced into a cell containing the target nucleic acid sequence, e. g., by formation of a polynucleotide-lipid complex, as described in WO 90/10448. It is understood that the use of antisense molecules or knock out and knock in models may also be used in screening assays as discussed above, in addition to methods of treatment.

Inhibitory and Antisense Nucleotides In certain embodiments, the activity of a cancer-associated protein is down-regulated, or entirely inhibited, by the use of antisense polynucleotide or inhibitory small nuclear RNA (snRNA), i. e., a nucleic acid complementary to, and which can preferably hybridize specifically to, a coding mRNA nucleic acid sequence, e. g., a cancer protein of the invention, mRNA, or a subsequence thereof. Binding of the antisense polynucleotide to the mRNA reduces the translation and/or stability of the mRNA.

In the context of this invention, antisense polynucleotides can comprise naturally occurring nucleotdes, or synthetic species formed from naturally occurring subunits or their close homologs. Antisense polynucleotides may also have altered sugar moieties or inter-sugar linkages. Exemplary among these are the phosphorothioate and other sulfur containing species which are known for use in the art. Analogs are comprised by this invention so long as they function effectively to hybridize with nucleotides of the invention. See, e. g., Isis Pharmaceuticals, Carlsbad, CA ; Sequitor, Inc., Natick, MA.

Such antisense polynucleotides can readily be synthesized using recombinant means, or can be synthesized in vitro. Equipment for such synthesis is sold by several vendors, including Applied Biosystems. The preparation of other oligonucleotides such as phosphorothioates and alkylated derivatives is also well known to those of skill in the art.

Antisense molecules as used herein include antisense or sense oligonucleotides. Sense oligonucleotides can, e. g., be employed to block transcription by binding to the anti-sense strand. The antisense and sense oligonucleotide comprise a single stranded nucleic acid sequence (either RNA or DNA) capable of binding to target mRNA (sense) or DNA (antisense) sequences for cancer molecules. Antisense or sense oligonucleotides, according to the present invention, comprise a fragment generally at least about 12 nucleotides, preferably from about 12 to 30 nucleotides. The ability to derive an antisense or a sense oligonucleotide, based upon a cDNA sequence encoding a given protein is described in, e. g., Stein &Cohen (Cancer Res. 48 : 2659 (1988 and van der Krol et al. (BioTechniques 6 : 958 (1988)).

Ribozymes In addition to antisense polynucleotides, ribozymes can be used to target and inhibit transcription of cancer- associated nucleotide sequences. A ribozyme is an RNA molecule that catalytically cleaves other RNA molecules. Different kinds of ribozymes have been described, including group I ribozymes, hammerhead ribozymes, hairpin ribozymes, RNase P, and axhead ribozymes (see, e. g., Castanotto et al., Adv. in Pharmacology 25 : 289-317 (1994) for a general review of the properties of different ribozymes).

The general features of hairpin ribozymes are described, e. g., in Hampel et al., Nucl. Acids Res. 18 : 299-304 (1990) ; European Patent Publication No. 0360257 ; U. S. Patent No. 5, 254, 678. Methods of preparing are well known to those of skill in the art (see, e. g., WO 94/26877 ; Ojwang et al., Proc. Natl. Acad. Sci. USA 90 : 6340-6344 (1993) ; Yamada et al., Human Gene Therapy 1 : 39-45 (1994) ; Leavitt et al., Proc. Natl. Acad Sci. USA 92 : 699- 703 (1995) ; Leavitt et al., Human Gene Therapy 5 : 1151-120 (1994) ; and Yamada et al., Virology 205 : 121-126 (1994)).

Use of Modulators in Phenotypic Screening In one embodiment, a test compound is administered to a population of cancer cells, which have an associated cancer expression profile. By"administration"or"contacting"herein is meant that the modulator is added to the cells in such a manner as to allow the modulator to act upon the cell, whether by uptake and intracellular action, or by action at the cell surface, In some embodiments, a nucleic acid encoding a proteinaceous agent (i. e., a peptide) is put into a viral construct such as an adenoviral or retroviral construct, and added to the cell, such that expression of the peptide agent is accomplished, e. g., PCT US97101019. Regulatable gene therapy systems can also be used. Once the modulator has been administered to the cells, the cells are washed if desired and are allowed to incubate under preferably physiological conditions for some period. The cells are then harvested and a new gene expression profile is generated. Thus, e. g., cancer tissue is screened for agents that modulate, e. g., induce or suppress, the cancer phenotype. A change in at least one gene, preferably many, of the expression profile indicates that the agent has an effect on cancer activity. Similarly, altering a biological function or a signaling pathway is indicative of modulator activity. By defining such a signature for the cancer phenotype, screens for new drugs that alter the phenotype are devised. With this approach, the drug target need not be known and need not be represented in the original gene/protein expression screening platform, nor does the level of transcript for the target protein need to change. The modulator inhibiting function will serve as a surrogate marker As outlined above, screens are done to assess genes or gene products. That is, having identified a particular differentially expressed gene as important in a particular state, screening of modulators of either the expression of the gene or the gene product itself is performed.

Use of Modulators to Affect Peptides of the invention Measurements of cancer polypeptide activity, or of the cancer phenotype are performed using a variety of assays.

For example, the effects of modulators upon the function of a cancer polypeptide (s) are measured by examining parameters described above. A physiological change that affects activity is used to assess the influence of a test compound on the polypeptides of this invention. When the functional outcomes are determined using intact cells or animals, a variety of effects can be assesses such as, in the case of a cancer associated with solid tumors, tumor growth, tumor metastasis, neovascularization, hormone release, transcriptional changes to both known and uncharacterized genetic markers (e. g., by Northern blots), changes in cell metabolism such as cell growth or pH changes, and changes in intracellular second messengers such as cGNIP.

Methods of identifying Characterizing Cancer-associated Sequences Expression of various gene sequences is correlated with cancer. Accordingly, disorders based on mutant or variant cancer genes are determined. In one embodiment, the invention provides methods for identifying cells containing variant cancer genes, e. g., determining the presence of, all or part, the sequence of at least one endogenous cancer gene in a cell. This is accomplished using any number of sequencing techniques. The invention comprises methods of identifying the cancer genotype of an individual, e. g., determining all or part of the sequence of at least one gene of the invention in the individual. This is generally done in at least one tissue of the individual, e. g., a tissue set forth in Table I, and may include the evaluation of a number of tissues or different samples of the same tissue. The method may include comparing the sequence of the sequenced gene to a known cancer gene, i. e., a wild-type gene to determine the presence of family members, homologies, mutations or variants. The sequence of all or part of the gene can then be compared to the sequence of a known cancer gene to determine if any differences exist. This is done using any number of known homology programs, such as BLAST, Bestfit, etc. The presence of a difference in the sequence between the cancer gene of the patient and the known cancer gene correlates with a disease state or a propensity for a disease state, as outlined herein.

In a preferred embodiment, the cancer genes are used as probes to determine the number of copies of the cancer gene in the genome. The cancer genes are used as probes to determine the chromosomal localization of the cancer genes.

Information such as chromosomal localization finds use in providing a diagnosis or prognosis in particular when chromosomal abnormalities such as translocations, and the like are identified in the cancer gene locus.

XIV.) KitslArticles of Manufacture For use in the laboratory, prognostic, prophylactic, diagnostic and therapeutic applications described herein, kits are within the scope of the invention. Such kits can comprise a carrier, package, or container that is compartmentalized to receive one or more containers such as vials, tubes, and the like, each of the container (s) comprising one of the separate elements to be used in the method, along with a label or insert comprising instructions for use, such as a use described herein. For example, the container (s) can comprise a probe that is or can be detectably labeled. Such probe can be an antibody or polynucleotide specific for a protein or a gene or message of the invention, respectively. Where the method utilizes nucleic acid hybridization to detect the target nucleic acid, the kit can also have containers containing nucleotide (s) for amplification of the target nucleic acid sequence. Kits can comprise a container comprising a reporter, such as a biotin- binding protein, such as avidin or streptavidin, bound to a reporter molecule, such as an enzymatic, fluorescent, or radioisotope label ; such a reporter can be used with, e. g., a nucleic acid or antibody. The kit can include all or part of the amino acid sequences in Figure 2 or Figure 3 or analogs thereof, or a nucleic acid molecule that encodes such amino acid sequences.

The kit of the invention will typically comprise the container described above and one or more other containers associated therewith that comprise materials desirable from a commercial and user standpoint, including buffers, diluents, filters, needles, syringes ; carrier, package, container, vial and/or tube labels listing contents and/or instructions for use, and package inserts with instructions for use.

A label can be present on or with the container to indicate that the composition is used for a specific therapy or non- therapeutic application, such as a prognostic, prophylactic, diagnostic or laboratory application, and can also indicate directions for either in vivo or in vitro use, such as those described herein. Directions and or other information can also be included on an insert (s) or label (s) which is included with or on the kit. The label can be on or associated with the container. A label a can be on a container when letters, numbers or other characters forming the label are molded or etched into the container itself ; a label can be associated with a container when it is present within a receptacle or carrier that also holds the container, e. g., as a package insert. The label can indicate that the composition is used for diagnosing, treating, prophylaxing or prognosing a condition, such as a neoplasia of a tissue set forth in Table f.

The terms"kit"and"article of manufacture"can be used as synonyms.

In another embodiment of the invention, an article (s) of manufacture containing compositions, such as amino acid sequence (s), small molecule (s), nucleic acid sequence (s), and/or antibody (s), e. g., materials useful for the diagnosis, prognosis, prophylaxis and/or treatment of neoplasias of tissues such as those set forth in Table I is provided. The article of manufacture typically comprises at least one container and at least one label. Suitable containers include, for example, bottles, vials, syringes, and test tubes. The containers can be formed from a variety of materials such as glass, metal or plastic. The container can hold amino acid sequence (s), small molecule (s), nucleic acid sequence (s), cell population (s) and/or antibody (s). In one embodiment, the container holds a polynucleotide for use in examining the mRNA expression profile of a cell, together with reagents used for this purpose. In another embodiment a container comprises an antibody, binding fragment thereof or specific binding protein for use in evaluating protein expression of109P1 D4 in cells and tissues, or for relevant laboratory, prognostic, diagnostic, prophylactic and therapeutic purposes ; indications and/or directions for such uses can be included on or with such container, as can reagents and other compositions or tools used for these purposes. In another embodiment, a container comprises materials for eliciting a cellular or humoral immune response, together with associated indications and/or directions. In another embodiment, a container comprises materials for adoptive immunotherapy, such as cytotoxic T cells (CTL) or helper T cells (HTL), together with associated indications and/or directions ; reagents and other compositions or tools used for such purpose can also be included.

The container can alternatively hold a composition that is effective for treating, diagnosis, prognosing or prophylaxing a condition and can have a sterile access port (for example the container can be an intravenous solution bag or a vial having a stopper pierceable by a hypodermic injection needle). The active agents in the composition can be an antibody capable of specifically binding 109P1 D4 and modulating the function of 109P1 D4.

The article of manufacture can further comprise a second container comprising a pharmaceutically-acceptable buffer, such as phosphate-buffered saline, Ringer's solution and/or dextrose solution. It can further include other materials desirable from a commercial and user standpoint, including other buffers, diluents, filters, stirrers, needles, syringes, and/or package inserts with indications and/or instructions for use.

EXAMPLES : Various aspects of the invention are further described and illustrated by way of the several examples that follow, none of which is intended to limit the scope of the invention.

Example 1 : SSH-Generated Isolation of cDNA Fragment of the 109P1 D4 Gene To isolate genes that are over-expressed in prostate cancer we used the Suppression Subtractive Hybridization (SSH) procedure using cDNA derived from prostate cancer tissues. The 109P1 D4 SSH cDNA sequence was from an experiment where cDNA derived from LNCaP cells that was androgen-deprived (by growing in the presence of charcoal-stripped serum) was subtracted from cDNA derived from LNCaP cells that were stimulated with mibolerone for 9 hours.

Materials and Methods Human Tissues : The patient cancer and normal tissues were purchased from different sources such as the NDRI (Philadelphia, PA). mRNA for some normal tissues were purchased from different companies such as Clontech, Palo Alto, CA.

RNA Isolation : Tissues were homogenized in Trizol reagent (Life Technologies, Gibco BRL) using 10 mll g tissue to isolate total RNA.

Poly A RNA was purified from total RNA using Qiagen's Oligotex mRNA Mini and Midi kits. Total and mRNA were quantified by spectrophotometric analysis (O. D. 260/280 nm) and analyzed by gel electrophoresis.

Oligonucleotides : The following HPLC purified oligonucleotides were used. DPNCDN (cDNA synthesis primer) : 5'TTTTGATCAAGCTT3o3' (SEQ ID NO : 44) Adaptor 1 : 5'CTAATACGACTCACTATAGGGCTCGAGCGGCCGCCCGGGCAG3' (SEQ ID NO : 45) 3'GGCCCGTCCTA135' (SEQ ID NO : 46) Adaptor 2 : 5'GTAATACGACTCACTATAGGGCAGCGTGGTCGCGGCCGAG3' (SEQ ID NO : 47) 3'CGGCTCCTAG5' (SEQ ID NO : 48) PCR primer 1 : 5'CTAATACGACTCACTATAGGGC3' (SEQ ID NO : 49) Nested primer (NP) 1 : 5'TCGAGCGGCCGCCCGGGCAGGA3' (SEQ ! D NO : 50) Nested primer (NP) 2 : 5'AGCGTGGTCGCGGCCGAGGA3' (SEQ ID NO : 51) Suppression Subtractive Hybridization : Suppression Subtractive Hybridization (SSH) was used to identify cDNAs corresponding to genes that may be differentially expressed in prostate cancer. The SSH reaction utilized cDNA from LNCaP prostate cancer cells.

The 109P1D4 SSH sequence was derived from cDNA subtraction of LNCaP stimulated with mibolerone minus LNCaP in the absence of androgen. The SSH DNA sequence (Figure 1) was identified.

The cDNA derived from androgen-deprived LNCaP cells was used as the source of the"driver"cDNA, while the cDNA from androgen-stimulated LNCaP cells was used as the source of the"tester"cDNA. Double stranded cDNAs corresponding to tester and driver cDNAs were synthesized from 2 ttg of poly (A) + RNA isolated from the relevant xenograft tissue, as described above, using CLONTECH's PCR-Select cDNA Subtraction Kit and 1 pg of oligonucleotide DPNCDN as primer. First-and second- strand synthesis were carried out as described in the Kit's user manual protocol (CLONTECH Protocol No. PT1117-1, Catalog No.

K1804-1). The resulting cDNA was digested with Dpn 11 for 3 hrs at 37oC. Digested cDNA was extracted with phenol/chloroform (1 : 1) and ethanol precipitated.

Tester cDNA was generated by diluting 1 gi of Dpn it digested cDNA from the relevant tissue source (see above) (400 ng) in 5 uI of water. The diluted cDNA (2 µl, 160 ng) was then ligated to 2 j'; of Adaptor 1 and Adaptor 2 (10 p^M), in separate ligation reactions, in a total volume of 10 pl at 16oC overnight, using 400 pi of T4 DNA ligase (CLONTECH). Ligation was terminated with 1 6tl of 0. 2 M EDTA and heating at 72OC for 5 min.

The first hybridization was performed by adding 1. 5 Kti (600 ng) of driver cDNA to each of two tubes containing 1. 5 µl (20 ng) Adaptor 1-and Adaptor 2-ligated tester cDNA. In a final volume of 4 Kti, the samples were overlaid with mineral oil, denatured in an MJ Research thermal cycler at 980C for 1. 5 minutes, and then were allowed to hybridize for 8 hrs at 68°C. The two hybridizations were then mixed together with an additional 1 µl of fresh denatured driver cDNA and were allowed to hybridize overnight at 68oC. The second hybridization was then diluted in 200 ul of 20 mM Hepes, pH 8. 3, 50 mM NaCi, 0. 2 mM EDTA, heated at 70OC for 7 min. and stored at-200C.

PCR Amplification, Cloning and Sequencing of Gene Fragments Generated from SSH : To amplify gene fragments resulting from SSH reactions, two PCR amplifications were performed. In the primary PCR reaction 1 µl of the diluted final hybridization mix was added to 1 ul of PCR primer 1 (10 Ils), 0. 5 pl dNTP mix (10 I1M), 2. 5 lli 10 x reaction buffer (CLONTECH) and 0. 5 pl 50 x Advantage cDNA polymerase Mix (CLONTECH) in a final volume of 25 lli. PCR 1 was conducted using the following conditions : 750C for 5 min., 94 (, C for 25 sec., then 27 cycles of 94oC for 10 sec, 66oC for 30 sec, 720C for 1. 5 min. Five separate primary PCR reactions were performed for each experiment. The products were pooled and diluted 1 : 10 with water. For the secondary PCR reaction, 1 RI from the pooled and diluted primary PCR reaction was added to the same reaction mix as used for PCR 1, except that primers NP1 and NP2 (10 M) were used instead of PCR primer 1. PCR 2 was performed using 10-12 cycles of 94tC for 10 sec, 680C for 30 sec, and 72oC for 1. 5 minutes. The PCR products were analyzed using 2% agarose gel electrophoresis.

The PCR products were inserted into pCR2. 1 using the T/A vector cloning kit (Invitrogen). Transformed E coli were subjected to blue/white and ampicillin selection. White colonies were picked and arrayed into 96 well plates and were grown in liquid culture overnight. To identify inserts, PCR amplification was performed on 1 uI of bacterial culture using the conditions of PCR1 and NP1 and NP2 as primers. PCR products were analyzed using 2% agarose gel electrophoresis.

Bacterial clones were stored in 20% glycerol in a 96 well format. Plasmid DNA was prepared, sequenced, and subjected to nucleic acid homology searches of the GenBank, dBest, and NCI-CGAP databases.

RT-PCR Expression Analysis : First strand cDNAs can be generated from 1 zu of mRNA with oligo (dT) 12-18 priming using the Gibco-BRL Superscript Preamplification system. The manufacturer's protocol was used which included an incubation for 50 min at 420C with reverse transcriptase followed by RNAse H treatment at 37oC for 20 min. After completing the reaction, the volume can be increased to 200 Rl with water prior to normalization. First strand cDNAs from 16 different normal human tissues can be obtained from Clontech.

Normalization of the first strand cDNAs from multiple tissues was performed by using the primers 5'ATATCGCCGCGCTCGTCGTCGACAA3' (SEQ ID NO : 52) and 5'AGCCACACGCAGCTCATTGTAGAAGG 3' (SEQ ID NO : 53) to amplify p-actin. First strand cDNAs (5 Ill) were amplified in a total volume of 50 Ill containing 0. 4 AM primers, 0. 2 PM each dNTPs, 1X PCR buffer (Clontech, 10 mM Tris-HCL, 1. 5 mM MgCl2, 50 mM KCI, pH8. 3) and 1X Klentaq DNA polymerase (Clontech). Five pl of the PCR reaction can be removed at 18, 20, and 22 cycles and used for agarose gel electrophoresis. PCR was performed using an MJ Research thermal cycler under the following conditions : Initial denaturation can be at 940C for 15 sec, followed by a 18, 20, and 22 cycles of 940C for 15, 650C for 2 min, 720C for 5 sec. A final extension at 720C was carried out for 2 min. After agarose gel electrophoresis, the band intensities of the 283 base pair p-actin bands from multiple tissues were compared by visual inspection. Dilution factors for the first strand cDNAs were calculated to result in equal ß-actin band intensities in all tissues after 22 cycles of PCR. Three rounds of normalization can be required to achieve equal band intensities in all tissues after 22 cycles of PCR.

To determine expression levels of the 109P1 D4 gene, 5 Ill of normalized first strand cDNA were analyzed by PCR using 26, and 30 cycles of amplification. Semi-quantitative expression analysis can be achieved by comparing the PCR products at cycle numbers that give light band intensities. The primers used for RT-PCR were designed using the 109P1D4 SSH sequence and are listed below : 109PI D4. 1 5'-TGGTCTTTCAGGTAATTGCTGTTG-3' (SEQ ID NO : 54) 109P1D4. 2 5'-CTCCATCAATGTTATGTTGCCTGT-3' (SEQ ID NO : 55) A typical RT-PCR expression analysis is shown in Figure 15.

Example 2 : Isolation of Full Length 109P1D4 encoding DNA The 109P1 D4 SSH sequence of 192 bp (Figure 1) exhibited homology to protocadherin 11 (PCDH11), acell adhesion molecule related to the calcium dependent cadherins. The human cDNA sequence encodes a 1021 amino acid protein with an N- terminal leader sequence and a transmembrane domain. 109P1D4 v. 1 of 4603bp was cloned from human prostate cancer xenograft LAPC-9AD cDNA library, revealing an ORF of 1021 amino acids (Figure 2 and Figure 3). Other variants (Transcript and SNP) of 109P1 D4 were also identified and these are listed sequentially in Figure 2 and Figure 3.

Example 3 : Chromosoma) Mapping of 109P1D4 Chromosomal localization can implicate genes in disease pathogenesis. Several chromosome mapping approaches are available including fluorescent in situ hybridization (FISH), human/hamster radiation hybrid (RH) panels (Walter et al., 1994 ; Nature Genetics 7 : 22 ; Research Genetics, Huntsville AI), human-rodent somatic cell hybrid panels such as is available from the Coriell Institute (Camden, New Jersey), and genomic viewers utilizing BLAST homologies to sequenced and mapped genomic clones (NCBI, Bethesda, Maryland).

109P1 D4 maps to chromosome Xq21. 3 using 109P1 D4 sequence and the NCBI BLAST tool : located on the World Wide Web at : (. ncbi. nlm. nih. gov/genome/seq/page. cgi ? F=HsBlast. html&&ORG=Hs). 109P1D4 was also identified on chromosome Yp11. 2, a region of 99% identity to Xq21.

Example 4 Expression Analysis of 109P1D4 in Normal Tissues and Patient Specimens Expression analysis by RT-PCR and Northern analysis demonstrated that normal tissue expression of a gene of Figure 2 is restricted predominantly to the tissues set forth in Table 1.

Therapeutic applications for a gene of Figure 2 include use as a small molecule therapy and/or a vaccine (T cell or antibody) target. Diagnostic applications for a gene of Figure 2 include use as a diagnostic marker for local and/or metastasized disease. The restricted expression of a gene of Figure 2 in normal tissues makes it useful as a tumor target for diagnosis and therapy. Expression analysis of a gene of Figure 2 provides information useful for predicting susceptibility to advanced stage disease, rate of progression, and/or tumor aggressiveness. Expression status of a gene of Figure 2 in patient samples, tissue arrays and/or cell lines may be analyzed by : (i) immunohistochemical analysis ; (ii) in situ hybridization ; (iii) RT-PCR analysis on laser capture micro-dissected samples ; (iv) Western blot analysis ; and (v) Northern analysis.

RT-PCR analysis and Northern blotting were used to evaluate gene expression in a selection of normal and cancerous urological tissues. The results are summarized in Figures 15-19.

Figure 14 shows expression of 109P1 D4 in lymphoma cancer patient specimens. RNA was extracted from peripheral blood lymphocytes, cord blood isolated from normal individuals, and from lymphoma patient cancer specimens.

Northern blots with 1 Opg of total RNA were probed with the 109P1 D4 sequence. Size standards in kilobases are on the side. Results show expression of 109P1 D4 in lymphoma patient specimens but not in the normal blood cells tested.

Figure 15 shows expression of 109P1 D4 by RT-PCR. First strand cDNA was prepared from vital pool 1 (liver, lung and kidney), vital pool 2 (pancreas, colon and stomach), prostate cancer pool, bladder cancer pool, kidney cancer pool, colon cancer pool, lung cancer pool, ovary cancer pool, breast cancer pool, cancer metastasis pool, and pancreas cancer pool. Normalization was performed by PCR using primers to actin and GAPDH. Semi-quantitative PCR, using primers to 109P1 D4, was performed at 30 cycles of amplification. Results show strong expression of 109P1 D4 in all cancer pools tested. Very low expression was detected in the vital pools.

Figure 16 shows expression of 109P1 D4 in normal tissues. Two multiple tissue northern blots (Clontech), both with 2 ug of mRNA/lane, were probed with the 109P1D4 SSH fragment. Size standards in kilobases (kb) are indicated on the side. Results show expression of approximately 10 kb 109P1D4 transcript in ovary. Weak expression was also detected in placenta and brain, but not in the other normal tissues tested.

Figure 17 shows expression of 109P1D4 in human cancer cell lines. RNA was extracted from a number of human prostate and bone cancer cell lines. Northern blots with 10 ug of total RNA/lane were probed with the 109P1 D4 SSH fragment. Size standards in kilobases (kb) are indicated on the side. Results show expression of 109P1D4 in LAPC-9AD, LAPC-9AI, LNCaP prostate cancer cell lines, and in the bone cancer cell lines, SK-ES-1 and RD-ES.

Extensive expression of 109P1 D4 in normal tissues is shown in Figure 18A. A cDNA dot blot containing 76 different samples from human tissues was analyzed using a 109P1 D4 SSH probe. Expression was only detected in multiple areas of the brain, placenta, ovary, and fetal brain, amongst all tissues tested.

Figure 18B shows expression of 109P1D4 in patient cancer specimens. Expression of 109P1D4 was assayed in a panel of human cancers (T) and their respective matched normal tissues (N) on RNA dot blots. Upregulated expression of 109P1 D4 in tumors compared to normal tissues was observed in uterus, lung and stomach. The expression detected in normal adjacent tissues (isolated from diseased tissues) but not in normal tissues (isolated from healthy donors) may indicate that these tissues are not fully normal and that 109P1 D4 may be expressed in early stage tumors.

Figure 19 shows 109P1 D4 expression in lung cancer patient specimens. RNA was extracted from normal lung, prostate cancer xenograft LAPC-9AD, bone cancer cell line RD-ES, and lung cancer patient tumors. Northern blots with 10 pg of total RNA were probed with 109P1 D4. Size standards in kilobases are on the side. Results show strong expression of 109P1 D4 in lung tumor tissues as well as the RD-ES cell line, but not in normal lung.

The restricted expression of 109P1 D4 in normal tissues and the expression detected in cancer patient specimens suggest that 109P1 D4 is a potential therapeutic target and a diagnostic marker for human cancers.

Example 5 : Splice Variants of 109P1 D4 Transcript variants are variants of mature mRNA from the same gene which arise by alternative transcription or alternative splicing. Alternative transcripts are transcripts from the same gene but start transcription at different points.

Splice variants are mRNA variants spliced differently from the same transcript. In eukaryotes, when a multi-exon gene is transcribed from genomic DNA, the initial RNA is spliced to produce functional mRNA, which has only exons and is used for translation into an amino acid sequence. Accordingly, a given gene can have zero to many alternative transcripts and each transcript can have zero to many splice variants. Each transcript variant has a unique exon makeup, and can have different coding and/or non-coding (5'or 3'end) portions, from the original transcript. Transcript variants can code for similar or different proteins with the same or a similar function or can encode proteins with different functions, and can be expressed in the same tissue at the same time, or in different tissues at the same time, or in the same tissue at different times, or in different tissues at different times. Proteins encoded by transcript variants can have similar or different cellular or extracellular localizations, e. g., secreted versus intracellular.

Transcript variants are identified by a variety of art-accepted methods. For example, alternative transcripts and splice variants are identified by full-length cloning experiment, or by use of full-length transcript and EST sequences. First, all human ESTs were grouped into clusters which show direct or indirect identity with each other. Second, ESTs in the same cluster were further grouped into sub-clusters and assembled into a consensus sequence. The original gene sequence is compared to the consensus sequence (s) or other full-length sequences. Each consensus sequence is a potential splice variant for that gene. Even when a variant is identified that is not a full-length clone, that portion of the variant is very useful for antigen generation and for further cloning of the full-length splice variant, using techniques known in the art.

Moreover, computer programs are available in the art that identify transcript variants based on genomic sequences. Genomic-based transcript variant identification programs include FgenesH (A. Salamov and V. Solovyev,"Ab initio gene finding in Drosophila genomic DNA,"Genome Research. 2000 April ; 10 (4) : 516-22) ; Grail (URL compbio. ornl. gov/Grail-bin/EmptyGrailForm) and GenScan (URL genes. mit. edu/GENSCAN. html). For a general discussion of splice variant identification protocols see., e. g., Southan, C., A genomic perspective on human proteases, FEBS Lett.

2001 Jun 8 ; 498 (2-3) : 214-8 ; de Souza, S. J., et al., identification of human chromosome 22 transcribed sequences with ORF expressed sequence tags, Proc. Natl Acad Sci U S A. 2000 Nov 7 ; 97 (23) : 12690-3.

To further confirm the parameters of a transcript variant, a variety of techniques are available in the art, such as full-length cloning, proteomic validation, PCR-based validation, and 5'RACE validation, etc. (see e. g., Proteomic Validation : Brennan, S. O., et al., Albumin banks peninsula : a new termination variant characterized by electrospray mass spectrometry, Biochem Biophys Acta. 1999 Aug 17 ; 1433 (1-2) : 321-6 ; Ferranti P, et al., Differential splicing of pre-messenger RNA produces multiple forms of mature caprine alpha (s1)-casein, Eur J Biochem. 1997 Oct 1 ; 249 (1) : 1-7. For PCR-based Validation : Wellmann S, et al., Specific reverse transcription-PCR quantification of vascular endothelial growth factor (VEGF) splice variants by LightCycler technology, Clin Chem. 2001 Apr ; 47 (4) : 654-60 ; Jia, H. P., et al., Discovery of new human beta- defensins using a genomics-based approach, Gene. 2001 Jan 24 ; 263 (1-2) : 211-8. For PCR-based and 5'RACE Validation : Brigle, K. E., et al., Organization of the murine reduced folate carrier gene and identification of variant splice forms, Biochem Biophys Acta. 1997 Aug 7 ; 1353 (2) : 191-8).

It is known in the art that genomic regions are modulated in cancers. When the genomic region to which a gene maps is modulated in a particular cancer, the alternative transcripts or splice variants of the gene are modulated as well.

Disclosed herein is that 109P1D4 has a particular expression profile related to cancer. Alternative transcripts and splice variants of 109P1D4 may also be involved in cancers in the same or different tissues, thus serving as tumor-associated markers/antigens.

Using the full-length gene and EST sequences, 8 transcript variants were identified, designated as 109P1D4 v. 2, v. 3, v. 4, v. 5, v. 6, v. 7, v. 8 and v. 9. The boundaries of the exon in the original transcript, 109P1D4 v. 1, were shown in Table Ll.

Compared with 109P1D4 v. 1, transcript variant 109P1D4 v. 3 has spliced out 2069-2395 from variant 109P1D4 v. 1, as shown in Figure 12. Variant 109P1D4 v. 4 spliced out 1162-2096 of variant 109P1D4 v. 1. Variant 109P1D4 v. 5 added one exon to the 5'and extended 2 bp to the 5'end and 288 bp to the 3'end of variant 109P1D4 v. 1. Theoretically, each different combination of exons in spatial order, e. g. exon 1 of v. 5 and exons 1 and 2 of v. 3 or v. 4, is a potential splice variant.

Tables LII through LV are set forth on a variant-by-variant basis. Tables Lll (a)- (h) show nucleotide sequence of the transcript variants. Tables LIII (a)- (h) show the alignment of the transcript variants with nucleic acid sequence of 109P1 D4 v. 1. Tables LIV (a)- (h) lay out amino acid translation of the transcript variants for the identified reading frame orientation. Tables LV (a)- (h) displays alignments of the amino acid sequence encoded by the splice variants with that of 109P1D4 v. 1.

Example 6 : Single Nucleotide Polymorphisms of 109P1D4 A Single Nucleotide Polymorphism (SNP) is a single base pair variation in a nucleotide sequence at a specific location. At any given point of the genome, there are four possible nucleotide base pairs : A/T, C/G, GIC and T/A. Genotype refers to the specific base pair sequence of one or more locations in the genome of an individual. Haplotype refers to the base pair sequence of more than one location on the same DNA molecule (or the same chromosome in higher organisms), often in the context of one gene or in the context of several tightly linked genes. SNP that occurs on a cDNA is called cSNP.

This cSNP may change amino acids of the protein encoded by the gene and thus change the functions of the protein. Some SNP cause inherited diseases ; others contribute to quantitative variations in phenotype and reactions to environmental factors including diet and drugs among individuals. Therefore, SNP and/or combinations of alleles (called haplotypes) have many applications, including diagnosis of inherited diseases, determination of drug reactions and dosage, identification of genes responsible for diseases, and analysis of the genetic relationship between individuals (P. Nowotny, J. M. Kwon and A.

M. Goate,"SNP analysis to dissect human traits,"Curr. Opin. Neurobiol. 2001 Oct ; 11 (5) : 637-641 ; M. Pirmohamed and B.

K. Park,"Genetic susceptibility to adverse drug reactions,"Trends Pharmacol. Sci. 2001 Jun ; 22 (6) : 298-305 ; J. H. Riley, C.

J. Allan, E. Lai and A. Roses,"The use of single nucleotide polymorphisms in the isolation of common disease genes," Pharmacogenomics. 2000 Feb ; 1 (1) : 39-47 ; R. Judson, J. C. Stephens and A. Windemuth,"The predictive power of haplotypes in clinical response,"Pharmacogenomics. 2000 Feb ; 1 (1) : 15-26).

SNP are identified by a variety of art-accepted methods (P. Bean,"The promising voyage of SNP target discovery," Am. Clin. Lab. 2001 Oct-Nov ; 20 (9) : 18-20 ; K. M. Weiss,"In search of human variation,"Genome Res. 1998 Jul ; 8 (7) : 691- 697 ; M. M. She,"Enabling large-scale pharmacogenetic studies by high-throughput mutation detection and genotyping technologies,"Clin. Chem. 2001 Feb ; 47 (2) : 164-172). For example, SNP can be identified by sequencing DNA fragments that show polymorphism by gel-based methods such as restriction fragment length polymorphism (RFLP) and denaturing gradient gel electrophoresis (DGGE). They can also be discovered by direct sequencing of DNA samples pooled from different individuals or by comparing sequences from different DNA samples. With the rapid accumulation of sequence data in public and private databases, one can discover SNP by comparing sequences using computer programs (Z. Gu, L. Hillier and P. Y. Kwok,"Single nucleotide polymorphism hunting in cyberspace,"Hum. Mutat. 1998 ; 12 (4) : 221-225). SNP can be verified and genotype or haplotype of an individual can be determined by a variety of methods including direct sequencing and high throughput microarrays (P. Y. Kwok,"Methods for genotyping single nucleotide polymorphisms,"Annu. Rev.

Genomics Hum. Genet. 2001 ; 2 : 235-258 ; M. Kokoris, K. Dix, K. Moynihan, J. Mathis, B. Erwin, P. Grass, B. Hines and A.

Duesterhoeft,"High-throughput SNP genotyping with the Masscode system,"Mol. Diagn. 2000 Dec ; 5 (4) : 329-340).

Using the methods described above, SNP were identified in the original transcript, 109P4D4 v. 1, and its variants (see Figure 2J and Figure 2K). These alleles of the SNP, though shown separately here, can occur in different combinations (haplotypes) and in any one of the transcript variants (such as 109P4D4 v. 4 or v. 5) that contains the site of the SNP.

Transcript variants v. 4 and v. 5 contained those SNP in the exons shared with variant v. 3, and transcript variant v. 9 contained all the SNP occurred in variant v. 6 (see Figure 10).

Example 7 : Production of Recombinant 109P1D4 in Prokaryotic Systems To express recombinant 109P1 D4 and 109PI D4 variants in prokaryotic cells, the full or partial length 109P1D4 and 109P1D4 variant cDNA sequences are cloned into any one of a variety of expression vectors known in the art. One or more of the following regions of 109P1 D4 variants are expressed : the full length sequence presented in Figures 2 and 3, or any 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 or more contiguous amino acids from 109P1D4, variants, or analogs thereof.

A. In vitro transcription and translation constructs : pCRII : To generate 109P1 D4 sense and anti-sense RNA probes for RNA in situ investigations, pCRll constructs (invitrogen, Carlsbad CA) are generated encoding either all or fragments of the 109P1 D4 cDNA. The pCRll vector has Sp6 and T7 promoters flanking the insert to drive the transcription of 109P1 D4 RNA for use as probes in RNA in situ hybridization experiments. These probes are used to analyze the cell and tissue expression of 109P1 D4 at the RNA level. Transcribed 109P1 D4 RNA representing the cDNA amino acid coding region of the 109P1 D4 gene is used in in vitro translation systems such as the TnTM Coupled Reticulolysate System (Promega, Corp., Madison, WI) to synthesize 109P1D4 protein.

B. Bacterial Constructs : pGEX Constructs : To generate recombinant 109P1D4 proteins in bacteria that are fused to the Glutathione S- transferase (GST) protein, all or parts of the 109P1 D4 cDNA protein coding sequence are cloned into the pGEX family of GST-fusion vectors (Amersham Pharmacia Biotech, Piscataway, NJ). These constructs allow controlled expression of recombinant 109P1 D4 protein sequences with GST fused at the amino-terminus and a six histidine epitope (6X His) at the carboxyl-terminus. The GST and 6X His tags permit purification of the recombinant fusion protein from induced bacteria with the appropriate affinity matrix and allow recognition of the fusion protein with anti-GST and anti-His antibodies. The 6X His tag is generated by adding 6 histidine codons to the cloning primer at the 3'end, e. g., of the open reading frame (ORF). A proteolytic cleavage site, such as the PreScissionTM recognition site in pGEX-6P-1, may be employed such that it permits cleavage of the GST tag from 109P1 D4-related protein. The ampicillin resistance gene and pBR322 origin permits selection and maintenance of the pGEX plasmids in E. coli. pMAL Constructs : To generate, in bacteria, recombinant 109P1D4 proteins that are fused to maltose-binding protein (MBP), all or parts of the 109P1 D4 cDNA protein coding sequence are fused to the MBP gene by cloning into the pMAL-c2X and pMAL-p2X vectors (New England Biolabs, Beverly, MA). These constructs allow controlled expression of recombinant 109P1D4 protein sequences with MBP fused at the amino-terminus and a 6X His epitope tag at the carboxyl- terminus. The MBP and 6X His tags permit purification of the recombinant protein from induced bacteria with the appropriate affinity matrix and allow recognition of the fusion protein with anti-MBP and anti-His antibodies. The 6X His epitope tag is generated by adding 6 histidine codons to the 3'cloning primer. A Factor Xa recognition site permits cleavage of the pMAL tag from 109P1D4. The pMAL-c2X and pMAL-p2X vectors are optimized to express the recombinant protein in the cytoplasm or periplasm respectively. Periplasm expression enhances folding of proteins with disulfide bonds. In one embodiment, amino acids 24-419 of 109P1D4 variant 1 was cloned into the pMAL-c2X vector and was used to express the fusion protein. pET Constructs : To express 109P1 D4 in bacterial cells, all or parts of the 109P1 D4 cDNA protein coding sequence are cloned into the pET family of vectors (Novagen, Madison, Wi). These vectors allow tightly controlled expression of recombinant 109P1 D4 protein in bacteria with and without fusion to proteins that enhance solubility, such as NusA and thioredoxin (Trx), and epitope tags, such as 6X His and S-Tag w that aid purification and detection of the recombinant protein. For example, constructs are made utilizing pET NusA fusion system 43. 1 such that regions of the 109P1 D4 protein are expressed as amino-terminal fusions to NusA. In 2 embodiments, amino acids 24-419 and 24-815 were cloned into pET43. 1 vector and used to express the fusion protein.

C. Yeast Constructs : pESC Constructs : To express 109P1 D4 in the yeast species Saccharomyces cerevisiae for generation of recombinant protein and functional studies, all or parts of the 109P1 D4 cDNA protein coding sequence are cloned into the pESC family of vectors each of which contain 1 of 4 selectable markers, HIS3, TRP1, LEU2, and URA3 (Stratagene, La Jolla, CA). These vectors allow controlled expression from the same plasmid of up to 2 different genes or cloned sequences containing either FlagTM or Myc epitope tags in the same yeast cell. This system is useful to confirm protein-protein interactions of 109P1 D4. In addition, expression in yeast yields similar post-translational modifications, such as glycosylations and phosphorylations, that are found when expressed in eukaryotic cells. pESP Constructs : To express 109P1 D4 in the yeast species Saccharomyces pombe, all or parts of the 109P1 D4 cDNA protein coding sequence are cloned into the pESP family of vectors. These vectors allow controlled high level of expression of a 109P1D4 protein sequence that is fused at either the amino terminus or at the carboxyl terminus to GST which aids purification of the recombinant protein. A FlagTM epitope tag allows detection of the recombinant protein with anti- Flag antibody.

Example 8 : Production of Recombinant 109P1 D4 in Higher Eukaryotic Systems A. Mamma n Construct : To express recombinant 109P1D4 in eukaryotic cells, the full or partial length 109P1D4 cDNA sequences were cloned into any one of a variety of expression vectors known in the art. One or more of the following regions of 109P1 D4 were expressed in these constructs, amino acids 1 to 1021 or any 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 or more contiguous amino acids from 109P1D4 v. 1 ; amino acids 1 to 1054, 1 to 1347, 1 to 1337, 1 to 1310, 1 to 1037, 1 to 1048, 1 to 1340 of v. 2, v. 3, v. 4, v. 5, v. 6, v. 7, and v. 8 respectively ; or any 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 or more contiguous amino acids from 109P1D4 variants, or analogs thereof.

The constructs can be transfected into any one of a wide variety of mammalian cells such as 293T cells.

Transfected 293T cell lysates can be probed with the anti-109P1D4 polyclonal serum, described herein. pcDNA4/HisMax Constructs : To express 109P1 D4 in mammalian cells, a 109P1D4 ORF, or portions thereof, of 109P1D4 are cloned into pcDNA4/HisMax Version A (Invitrogen, Carlsbad, CA). Protein expression is driven from the cytomegalovirus (CMV) promoter and the SP16 translational enhancer. The recombinant protein has XpressTM and six histidine (6X His) epitopes fused to the amino-terminus. The pcDNA4/HisMax vector also contains the bovine growth hormone (BGH) polyadenylation signal and transcription termination sequence to enhance mRNA stability along with the SV40 origin for episomal replication and simple vector rescue in cell lines expressing the large T antigen. The Zeocin resistance gene allows for selection of mammalian cells expressing the protein and the ampicillin resistance gene and ColE1 origin permits selection and maintenance of the plasmid in E. coli. pcDNA3. 11MycHis Constructs : To express 109P1D4 in mammalian cells, a 109P1D4 ORF, or portions thereof, of 109P1D4 with a consensus Kozak translation initiation site was cloned into pcDNA3. 1/MycHis Version A (Invitrogen, Carlsbad, CA). Protein expression is driven from the cytomegalovirus (CMV) promoter. The recombinant proteins have the myc epitope and 6X His epitope fused to the carboxyl-terminus. The pcDNA3. 1/MycHis vector also contains the bovine growth hormone (BGH) polyadenylation signal and transcription termination sequence to enhance mRNA stability, along with the SV40 origin for episomal replication and simple vector rescue in cell lines expressing the large T antigen. The Neomycin resistance gene can be used, as it allows for selection of mammalian cells expressing the protein and the ampicillin resistance gene and ColE1 origin permits selection and maintenance of the plasmid in E coli.

The complete ORF of 109P1D4 v. 1 was cloned into the pcDNA3. 1/MycHis construct to generate 109PI D4. pcDNA3. 1/MycHis. pcDNA3. 1/CT-GFP-TOPO Construct : To express 109P1D4 in mammalian cells and to allow detection of the recombinant proteins using fluorescence, a 109P1D4 ORF, or portions thereof, with a consensus Kozak translation initiation site are cloned into pcDNA3. 1/CT-GFP-TOPO (Invitrogen, CA). Protein expression is driven from the cytomegalovirus (CMV) promoter. The recombinant proteins have the Green Fluorescent Protein (GFP) fused to the carboxyl-terminus facilitating non-invasive, in vivo detection and cell biology studies. The pcDNA3. 1 CT-GFP-TOPO vector also contains the bovine growth hormone (BGH) polyadenylation signal and transcription termination sequence to enhance mRNA stability along with the SV40 origin for episomal replication and simple vector rescue in cell lines expressing the large T antigen. The Neomycin resistance gene allows for selection of mammalian cells that express the protein, and the ampicillin resistance gene and ColE1 origin permits selection and maintenance of the plasmid in E coli. Additional constructs with an amino- terminal GFP fusion are made in pcDNA3. 1/NT-GFP-TOPO spanning the entire length of a 109P1D4 protein.

PA_ Ptaa : A 109P1 D4 ORF, or portions thereof, is cloned into pAPtag-5 (GenHunter Corp. Nashville, TN). This construct generates an alkaline phosphatase fusion at the carboxyl-terminus of a 109P1 D4 protein while fusing the lgGlc signal sequence to the amino-terminus. Constructs are also generated in which aikaiine phosphatase with an amino- terminal IgGK signal sequence is fused to the amino-terminus of a 109P1D4 protein. The resulting recombinant 109P1 D4 proteins are optimized for secretion into the media of transfected mammalian cells and can be used to identify proteins such as ligands or receptors that interact with 109P1 D4 proteins. Protein expression is driven from the CMV promoter and the recombinant proteins also contain myc and 6X His epitopes fused at the carboxyl-terminus that facilitates detection and purification. The Zeocin resistance gene present in the vector allows for selection of mammalian cells expressing the recombinant protein and the ampicillin resistance gene permits selection of the plasmid in E coli.

Tp ag5 : A 109P1 D4 ORF, or portions thereof, were cloned into pTag-5. This vector is similar to pAPtag but without the alkaline phosphatase fusion. This construct generated 109P1 D4 protein with an amino-terminal IgGr, signal sequence and myc and 6X His epitope tags at the carboxyl-terminus that facilitate detection and affinity purification. The resulting recombinant 109P1 D4 protein was optimized for secretion into the media of transfected mammalian cells, and was used as immunogen or ligand to identify proteins such as ligands or receptors that interact with the 109P1 D4 proteins.

Protein expression is driven from the CMV promoter. The Zeocin resistance gene present in the vector allows for selection of mammalian cells expressing the protein, and the ampicillin resistance gene permits selection of the plasmid in E. coti.

PsecFc : A 109P1D4 ORF, or portions thereof, is also cloned into psecFc. The psecFc vector was assembled by cloning the human immunoglobulin G1 (IgG) Fc (hinge, CH2, CH3 regions) into pSecTag2 (Invitrogen, California). This construct generates an IgG1 Fc fusion at the carboxyl-terminus of the 109P1 D4 proteins, while fusing the IgGK signal sequence to N-terminus. 109P1 D4 fusions utilizing the murine IgG1 Fc region are also used. The resulting recombinant 109P1D4 proteins are optimized for secretion into the media of transfected mammalian cells, and can be used as immunogens or to identify proteins such as ligands or receptors that interact with 109P1 D4 protein. Protein expression is driven from the CMV promoter. The hygromycin resistance gene present in the vector allows for selection of mammalian cells that express the recombinant protein, and the ampicillin resistance gene permits selection of the plasmid in E coli. pSRa Constructs : To generate mammalian cell lines that express 109P1 D4 constitutively, 109P1 D4 ORF, or portions thereof, were cloned into pSRa constructs. Amphotropic and ecotropic retroviruses were generated by transfection of pSRa constructs into the 293T-10A1 packaging line or co-transfection of pSRa and a helper plasmid (containing deleted packaging sequences) into the 293 cells, respectively. The retrovirus is used to infect a variety of mammalian cell lines, resulting in the integration of the cloned gene, 109P1 D4, into the host cell-lines. Protein expression is driven from a long terminal repeat (LTR). The Neomycin resistance gene present in the vector allows for selection of mammalian cells that express the protein, and the ampicillin resistance gene and ColE1 origin permit selection and maintenance of the plasmid in E coli. The retroviral vectors can thereafter be used for infection and generation of various cell lines using, for example, PC3, NIH 3T3, TsuPrl, 293 or rat-1 cells.

Additional pSRa constructs are made that fuse an epitope tag such as the FLAGTM tag to the carboxyl-terminus of 109P1 D4 sequences to allow detection using anti-Flag antibodies. For example, the FLAGTM sequence 5'GAT TAC AAG GAT GAC GAC GAT AAG 3' (SEQ ID NO : 56) is added to cloning primer at the 3'end of the ORF. Additional pSRa constructs are made to produce both amino-terminal and carboxyl-terminal GFP and myc/6X His fusion proteins of the full- length 109P1 D4 proteins.

Additional Viral Vectors : Additional constructs are made for viral-mediated delivery and expression of 109P1D4.

High virus titer leading to high level expression of 109P1 D4 is achieved in viral delivery systems such as adenoviral vectors and herpes amplicon vectors. A 109P1D4 coding sequence or fragments thereof are amplified by PCR and subcloned into the AdEasy shuttle vector (Stratagene). Recombination and virus packaging are performed according to the manufacturer's instructions to generate adenoviral vectors. Alternatively, 109P1 D4 coding sequences or fragments thereof are cloned into the HSV-1 vector (Imgenex) to generate herpes viral vectors. The viral vectors are thereafter used for infection of various cell lines such as PC3, NIH 3T3, 293 or rat-1 cells.

Regulated Expression Systems : To control expression of 109P1D4 in mammalian cells, coding sequences of 109P1D4, or portions thereof, are cloned into regulated mammalian expression systems such as the T-Rex System (Invitrogen), the GeneSwitch System (Invitrogen) and the tightly-regulated Ecdysone System (Stratagene). These systems allow the study of the temporal and concentration dependent effects of recombinant 109P1 D4. These vectors are thereafter used to control expression of 109P1D4 in various cell lines such as PC3, NIH 3T3, 293 or rat-1 cells.

B. Baculovirus Expression Systems To generate recombinant 109P1D4 proteins in a baculovirus expression system, 109P1 D4 ORF, or portions thereof, are cloned into the baculovirus transfer vector pBlueBac 4. 5 (Invitrogen), which provides a His-tag at the N-terminus.

Specifically, pBlueBac-1 09P1 D4 is co-transfected with helper plasmid pBac-N-Blue (invitrogen) into SF9 (Spodoptera frugiperda) insect cells to generate recombinant baculovirus (see Invitrogen instruction manual for details). Baculovirus is then collected from cell supernatant and purified by plaque assay.

Recombinant 109P1 D4 protein is then generated by infection of HighFive insect cells (Invitrogen) with purified baculovirus. Recombinant 109P1D4 protein can be detected using anti-109PlD4 or anti-His-tag antibody. 109P1D4 protein can be purified and used in various cell-based assays or as immunogen to generate polyclonal and monoclonal antibodies specific for 109PI D4.

Example 9 : Antigenicity Profiles and Secondary Structure Figure (s) 5A-I, Figure 6A-I, Figure 7A-I Figure 8A-I, and Figure 9A-I depict graphically five amino acid profiles of 109P1D4 variants 1 through 9, each assessment available by accessing the ProtScale website located on the World Wide Web at (. expasy. ch/cgi-bin/protscale. pi) on the ExPasy molecular biology server.

These profiles : Figure 5, Hydrophilicity, (Hopp T. P., Woods K. R., 1981. Proc. Natl. Acad. Sci. U. S. A. 78 : 3824- 3828) ; Figure 6, Hydropathicity, (Kyte J., Doolittle R. F., 1982. J. Mol. Biol. 157 : 105-132) ; Figure 7, Percentage Accessible Residues (Janin J., 1979 Nature 277 : 491-492) ; Figure 8, Average Flexibility, (Bhaskaran R., and Ponnuswamy P. K., 1988. lnt. J. Pept. Protein Res. 32 : 242-255) ; Figure 9, Beta-turn (Deleage, G., Roux B. 1987 Protein Engineering 1 : 289-294) ; and optionally others available in the art, such as on the ProtScale website, were used to identify antigenic regions of each of the 109P1D4 variant proteins. Each of the above amino acid profiles of 109P1 D4 variants were generated using the following ProtScale parameters for analysis : 1) A window size of 9 ; 2) 100% weight of the window edges compared to the window center ; and, 3) amino acid profile values normalized to lie between 0 and 1.

Hydrophilicity (Figure 5), Hydropathicity (Figure 6) and Percentage Accessible Residues (Figure 7) profiles were used to determine stretches of hydrophilic amino acids (i. e., values greater than 0. 5 on the Hydrophilicity and Percentage Accessible Residues profile, and values less than 0. 5 on the Hydropathicity profile). Such regions are likely to be exposed to the aqueous environment, be present on the surface of the protein, and thus available for immune recognition, such as by antibodies.

Average Flexibility (Figure 8) and Beta-turn (Figure 9) profiles determine stretches of amino acids (i. e., values greater than 0. 5 on the Beta-turn profile and the Average Flexibility profile) that are not constrained in secondary structures such as beta sheets and alpha helices. Such regions are also more likely to be exposed on the protein and thus accessible to immune recognition, such as by antibodies.

Antigenic sequences of the 109P1 D4 variant proteins indicated, e. g., by the profiles set forth in Figure 5, Figure 6, Figure 7, Figure 8, and/or Figure 9 are used to prepare immunogens, either peptides or nucleic acids that encode them, to generate therapeutic and diagnostic anti-109PD4 antibodies. The immunogen can be any 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 30, 35, 40, 45, 50 or more than 50 contiguous amino acids, or the corresponding nucleic acids that encode them, from the 109PI D4 protein variants listed in Figures 2 and 3. In particular, peptide immunogens of the invention can comprise, a peptide region of at least 5 amino acids of Figures 2 and 3 in any whole number increment that includes an amino acid position having a value greater than 0. 5 in the Hydrophilicity profiles of Figure 5 ; a peptide region of at least 5 amino acids of Figures 2 and 3 in any whole number increment that includes an amino acid position having a value less than 0. 5 in the Hydropathicity profile of Figure 6 ; a peptide region of at least 5 amino acids of Figures 2 and 3 in any whole number increment that includes an amino acid position having a value greater than 0. 5 in the Percent Accessible Residues profiles of Figure 7 ; a peptide region of at least 5 amino acids of Figures 2 and 3 in any whole number increment that includes an amino acid position having a value greater than 0. 5 in the Average Flexibility profiles on Figure 8 ; and, a peptide region of at least 5 amino acids of Figures 2 and 3 in any whole number increment that includes an amino acid position having a value greater than 0. 5 in the Beta-turn profile of Figures 9. Peptide immunogens of the invention can also comprise nucleic acids that encode any of the forgoing.

All immunogens of the invention, peptide or nucleic acid, can be embodied in human unit dose form, or comprised by a composition that includes a pharmaceutical excipient compatible with human physiology.

The secondary structure of 109P1D4 protein variants, namely the predicted presence and location of alpha helices, extended strands, and random coils, are predicted from the primary amino acid sequence using the HNN-Hierarchical Neural Network method (NPS@ : Network Protein Sequence Analysis TfBS 2000 March Vol. 25, No 3 [291] : 147-150 Combet C., Blanchet C., Geourjon C. and Deleage G., http ://pbil. ibCp. fr1cgi-bin/npsa_automat. pl ? page=npsa_nn. html), accessed from the ExPasy molecular biology server located on the World Wide Web at (www. expasy. ch/tools/). This analysis for protein variants 1 through 9 are shown in Figure 13A through 131 respectively. The percent of structure for each variant comprised of alpha helix, extended strand, and random coil is also indicated.

Analysis for the potential presence of transmembrane domains in 109P1 D4 variant proteins was carried out using a variety of transmembrane prediction algorithms accessed from the ExPasy molecular biology server located on the World Wide Web at (www. expasy. ch/tools/). Shown graphically in figures 13J-R are the results of analyses using the TMpred program (top panels) and the TMHMM program (bottom panels) of 109P1D4 protein variants 1 through 9 respectively.

Analyses of the variants using other structural prediction programs are summarized in Table Vi and Table L.

Example 10 : Generation of 109P1D4 Polyclonal Antibodies Polyclonal antibodies can be raised in a mammal, for example, by one or more injections of an immunizing agent and, if desired, an adjuvant. Typically, the immunizing agent and/or adjuvant will be injected in the mammal by multiple subcutaneous or intraperitoneal injections. In addition to immunizing with a full length 109P1D4 protein variant, computer algorithms are employed in design of immunogens that, based on amino acid sequence analysis contain characteristics of being antigenic and available for recognition by the immune system of the immunized host (see the Example entitled "Antigenicity Profiles and Secondary Structure"). Such regions would be predicted to be hydrophilic, flexible, in beta-turn conformations, and be exposed on the surface of the protein (see, e. g., Figure 5, Figure 6, Figure 7, Figure 8, or Figure 9 for amino acid profiles that indicate such regions of 109P1D4 protein variant 1).

For example, recombinant bacterial fusion proteins or peptides containing hydrophilic, flexible, beta-turn regions of 109P1D4 protein variants are used as antigens to generate polydonal antibodies in New Zealand White rabbits or monoclonal antibodies as described in the example entitled"Generation of 109PI D4 Monoclonal Antibodies (mAbs)". For example, in 109P1D4 variant 1, such regions include, but are not limited to, amino acids 22-39, amino acids 67-108, amino acids 200-232, amino acids 454-499, amino acids 525-537, amino acids 640-660, amino acids 834-880, and amino acids 929-942. It is useful to conjugate the immunizing agent to a protein known to be immunogenic in the mammal being immunized. Examples of such immunogenic proteins include, but are not limited to, keyhole limpet hemocyanin (KLH), serum albumin, bovine thyroglobulin, and soybean trypsin inhibitor. In 2 embodiments, peptides encoding amino acids 77-90 and amino acids 929-942 of 109P1D4 variant 1 were synthesized, conjugated to KLH, and used to immunize separate rabbits. Alternatively the immunizing agent may include all or portions of the 109P1 D4 variant proteins, analogs or fusion proteins thereof. For example, the 109P1 D4 variant 1 amino acid sequence can be fused using recombinant DNA techniques to any one of a variety of fusion protein partners that are well known in the art, such as glutathione-S-transferase (GST) and HIS tagged fusion proteins. In 1 embodiment, amino acids 24-419 of 109P1D4 variant 1 was fused to NUSa using recombinant techniques and the pET43. 1 expression vector, expressed, purified and used to immunize a rabbit. Such fusion proteins are purified from induced bacteria using the appropriate affinity matrix.

Other recombinant bacterial fusion proteins that may be employed include maltose binding protein, LacZ, thioredoxin, NusA, or an immunoglobulin constant region (see the section entitled"Production of 109P1D4 in Prokaryotic Systems"and Current Protocols In Molecular Biology, Volume 2, Unit 16, Frederick M. Ausubul et al. eds., 1995 ; Linsley, P. S., Brady, W., Urnes, M., Grosmaire, L., Damle, N., and Ledbetter, J. (1991) J. Exp. Med. 174, 561-566).

In addition to bacterial derived fusion proteins, mammalian expressed protein antigens are also used. These antigens are expressed from mammalian expression vectors such as the Tag5 and Fc-fusion vectors (see the section entitled"Production of Recombinant 109P1D4 in Eukaryotic Systems"), and retain post-translational modifications such as glycosylations found in native protein. In one embodiment, amino acids 24-812 of 109P1 D4 variant 1 was cloned into the Tag5 mammalian secretion vector, and expressed in 293T cells (See Figure 20). The recombinant protein is purified by metal chelate chromatography from tissue culture supernatants of 293T cells stably expressing the recombinant vector. The purified Tag5109P1D4 protein is then used as immunogen.

During the immunization protocol, it is useful to mix or emulsify the antigen in adjuvants that enhance the immune response of the host animal. Examples of adjuvants include, but are not limited to, complete Freund's adjuvant (CFA) and MPL-TDM adjuvant (monophosphoryl Lipid A, synthetic trehalose dicorynomycolate).

In a typical protocol, rabbits are initially immunized subcutaneously with up to 200 jug, typically 100-200 gg, of fusion protein or peptide conjugated to KLH mixed in complete Freund's adjuvant (CFA). Rabbits are then injected subcutaneously every two weeks with up to 200 p. g, typically 100-200 lAg, of the immunogen in incomplete Freund's adjuvant (IFA). Test bleeds are taken approximately 7-10 days following each immunization and used to monitor the titer of the antiserum by ELISA.

To test reactivity and specificity of immune serum, such as the rabbit serum derived from immunization with the NUSa-fusion of 109P1D4 variant 1 protein, the full-length 109P1 D4 variant 1 cDNA is cloned into pCDNA 3. 1 myc-his expression vector (Invitrogen, see the Example entitled"Production of Recombinant 109P1 D4 in Eukaryotic Systems"). After transfection of the constructs into 293T cells, cell lysates are probed with the anti-109P1 D4 serum to determine specific reactivity to denatured 109P1D4 protein using the Western blot technique. Probing with anti-His antibody serves as a positive control for expression of 109P1D4 in the transfected cells (See Figure 21). In addition, the immune serum is tested by fluorescence microscopy, flow cytometry and immunoprecipitation against 293T and other recombinant 109P1 D4- expressing cells to determine specific recognition of native protein. Western blot, immunoprecipitation, fluorescent microscopy, and flow cytometric techniques using cells that endogenously express 109P1 D4 are also carried out to test reactivity and specificity.

Anti-serum from rabbits immunized with 109P1 D variant fusion proteins, such as GST and MBP fusion proteins, are purified by depletion of antibodies reactive to the fusion partner sequence by passage over an affinity column containing the fusion partner either alone or in the context of an irrelevant fusion protein. For example, antiserum derived from a NUSa- 109P1D4 variant 1 fusion protein is first purified by passage over a column of MBP protein covalently coupled to AffiGel matrix (BioRad, Hercules, Calif.). The antiserum is then affinity purified by passage over a column composed of a NUSa- 109P1D4 fusion protein covalently coupled to Affigel matrix. The serum is then further purified by protein G affinity chromatography to isolate the gG fraction. Sera from other His-tagged antigens and peptide immunized rabbits as well as fusion partner depleted sera are affinity purified by passage over a column matrix composed of the original protein immunogen or free peptide.

Example 11 : Generation of 109P1D4 Monoclonal Antibodies (mAbs) In one embodiment, therapeutic mAbs to 109P1 D4 variants comprise those that react with epitopes specific for each variant protein or specific to sequences in common between the variants that would disrupt or modulate the biological function of the 109P1 D4 variants, for example those that would disrupt the interaction with ligands and binding partners.

Immunogens for generation of such mAbs include those designed to encode or contain the entire 109P1 D4 protein variant sequence, regions predicted to contain functional motifs, and regions of the 109P1D4 protein variants predicted to be antigenic from computer analysis of the amino acid sequence (see, e. g., Figure 5, Figure 6, Figure 7, Figure 8, or Figure 9, and the Example entitled"Antigenicity Profiles and Secondary Structure"). mmunogens include peptides, recombinant bacterial proteins, and mammalian expressed Tag 5 proteins and human and murine gG FC fusion proteins. In addition, cells engineered to express high levels of a respective 109P1D4 variant, such as 293T-109P1D4 variant 1 or 300. 19- 109P1D4 variant 1 murine Pre-B cells, are used to immunize mice.

To generate mAbs to a 109P1 D4 variant, mice are first immunized intraperitoneally (IP) with, typically, 10-50 ig of protein immunogen or 107109P1D4-expressing cel, s mixed in complete Freund's adjuvant. Mice are then subsequently immunized IP every 2-4 weeks with, typically, 10-50 g of protein immunogen or 107 cells mixed in incomplete Freund's adjuvant. Alternatively, MPL-TDM adjuvant is used in immunizations. In addition to the above protein and cell-based immunization strategies, a DNA-based immunization protocol is employed in which a mammalian expression vector encoding a 109P1 D4 variant sequence is used to immunize mice by direct injection of the plasmid DNA. For example, amino acids 24-812 of 109P1 D4 of variant 1 is cloned into the Tag5 mammalian secretion vector and the recombinant vector will then be used as immunogen. In another example the same amino acids are cloned into an Fc-fusion secretion vector in which the 109P1 D4 variant 1 sequence is fused at the amino-terminus to an IgK leader sequence and at the carboxyl- terminus to the coding sequence of the human or murine IgG Fc region. This recombinant vector is then used as immunogen. The plasmid immunization protocols are used in combination with purified proteins expressed from the same vector and with cells expressing the respective 109P1D4 variant.

Alternatively, mice may be immunized directly into their footpads. In this case, 10-50 pg of protein immunogen or 107 254P1 D6B-expressing cells are injected sub-cutaneously into the footpad of each hind leg. The first immunization is given with Titermax (Sigma) as an adjuvant and subsequent injections are given with Alum-gel in conjunction with CpG oligonucleotide sequences with the exception of the final injection which is given with PBS. Injections are given twice weekly (every three to four days) for a period of 4 weeks and mice are sacrificed 3-4 days after the final injection, at which point lymph nodes immediately draining from the footpad are harvested and the B-cells are collected for use as antibody producing fusion partners.

During the immunization protocol, test bleeds are taken 7-10 days following an injection to monitor titer and specificity of the immune response. Once appropriate reactivity and specificity is obtained as determined by ELISA, Western blotting, immunoprecipitation, fluorescence microscopy, and flow cytometric analyses, fusion and hybridoma generation is then carried out with established procedures well known in the art (see, e. g., Harlow and Lane, 1988).

In one embodiment for generating 109P1 D4 monoclonal antibodies, a Tag5 antigen of variant 1 encoding amino acids 14-812 is expressed in 293T cells and purified from conditioned media. Balb C mice are initially immunized intraperitoneally with 25 gag of the Tag5 1 09P1 M variant 1 protein mixed in complete Freund's adjuvant. Mice are subsequently immunized every two weeks with 25 gg of the antigen mixed in incomplete Freund's adjuvant for a total of three immunizations. ELISA using the Tag5 antigen determines the titer of serum from immunized mice. Reactivity and specificity of serum to full length 109P1D4 variant 1 protein is monitored by Western blotting, immunoprecipitation and flow cytometry using 293T cells transfected with an expression vector encoding the 109P1D4 variant 1 cDNA (see e. g., the Example entitled"Production of Recombinant 109P1D4 in Higher Eukaryotic Systems"and Figure 21). Other recombinant 109P1D4 variant 1-expressing cells or cells endogenous, y expressing 109P1D4 variant 1 are also used. Mice showing the strongest reactivity are rested and given a final injection of antigen in PBS and then sacrificed four days later. The spleens of the sacrificed mice are harvested and fused to SPO/2 myeloma cells using standard procedures (Harlow and Lane, 1988).

Supernatants from HAT selected growth wells are screened by ELISA, Western blot, immunoprecipitation, fluorescent microscopy, and flow cytometry to identify 109P1D4 specific antibody-producing clones.

To generate monoclonal antibodies that are specific for a 109P1D4 variant protein, immunogens are designed to encode sequences unique for each variant. In one embodiment, an antigenic peptide composed of amino acids 1-29 of 109P1D4 variant 2 is coupled to KLH to derive monoclonal antibodies specific to 109P1D4 variant 2. in another embodiment, an antigenic peptide comprised of amino acids 1-23 of 109P1 D4 variant 6 is coupled to KLH and used as immunogen to derive variant 6 specific MAbs. In another example, a GST-fusion protein encoding amino acids 1001-1347 of variant 3 is used as immunogen to generate antibodies that would recognize variants 3, 4, 5, and 8, and distinguish them from variants 1, 2, 6, 7and 9. Hybridoma supernatants are then screened on the respective antigen and then further screened on cells expressing the specific variant and cross-screened on cells expressing the other variants to derive variant- specific monoclonal antibodies.

The binding affinity of 109P1D4 variant specific monoclonal antibodies are determined using standard technologies. Affinity measurements quantify the strength of antibody to epitope binding and are used to help define which 109P1 D4 variant monoclonal antibodies preferred for diagnostic or therapeutic use, as appreciated by one of skill in the art.

The BIAcore system (Uppsala, Sweden) is a preferred method for determining binding affinity. The BlAcore system uses surface plasmon resonance (SPR, Welford K. 1991, Opt. Quant. Elect. 23 : 1 ; Morton and Myszka, 1998, Methods in Enzymology 295 : 268) to monitor biomolecular interactions in real time. BlAcore analysis conveniently generates association rate constants, dissociation rate constants, equilibrium dissociation constants, and affinity constants.

Alternatively, equilibrium binding analysis of MAbs on 109P1 D4-expressing cells can be used to determine affinity.

Example 12 : HLA Oass) and Oass)) Binding Assays HLA class I and class 11 binding assays using purified HLA molecules are performed in accordance with disclosed protocols (e. g., PCT publications WO 94/20127 and WO 94/03205 ; Sidney et al., Current Protocols in Immunology 18. 3. 1 (1998) ; Sidney, et al., J. Immunol. 154 : 247 (1995) ; Sette, et a/., Mol. Immunol. 31 : 813 (1994)). Briefly, purified MHC molecules (5 to 500 nM) are incubated with various unlabeled peptide inhibitors and 1-10 nM 1251-radiolabeled probe peptides as described. Following incubation, MHC-peptide complexes are separated from free peptide by gel filtration and the fraction of peptide bound is determined. Typically, in preliminary experiments, each MHC preparation is titered in the presence of fixed amounts of radiolabeled peptides to determine the concentration of HLA molecules necessary to bind 10- 20% of the total radioactivity. All subsequent inhibition and direct binding assays are performed using these HLA concentrations.

Since under these conditions [iabei] < [HLA] and iCso [HLA], the measured Cso values are reasonable approximations of the true Ko values. Peptide inhibitors are typically tested at concentrations ranging from 120 lig/m, to 1. 2 ng/ml, and are tested in two to four completely independent experiments. To allow comparison of the data obtained in different experiments, a relative binding figure is calculated for each peptide by dividing the Cso of a positive control for inhibition by the ICso for each tested peptide (typically unlabeled versions of the radiolabeled probe peptide). For database purposes, and inter-experiment comparisons, relative binding values are compiled. These values can subsequently be converted back into C50 nM values by dividing the ! Cso nM of the positive controls for inhibition by the relative binding of the peptide of interest. This method of data compilation is accurate and consistent for comparing peptides that have been tested on different days, or with different lots of purified MHC.

Binding assays as outlined above may be used to analyze HLA supermotif and/or HLA motif-bearing peptides (see Table IV).

Example 13 : Identification of HLA Supermotif-and Motif-Bearing CTL Candidate Epitopes HLA vaccine compositions of the invention can include multiple epitopes. The multiple epitopes can comprise multiple HLA supermotifs or motifs to achieve broad population coverage. This example illustrates the identification and confirmation of supermotif-and motif-bearing epitopes for the inclusion in such a vaccine composition. Calculation of population coverage is performed using the strategy described below.

Computer searches and algorithms for identification of supermotif and/or motif-bearing epitopes The searches performed to identify the motif-bearing peptide sequences in the Example entitled"Antigenicity Profiles"and Tables VIII-XXI and XXII-XLIX employ the protein sequence data from the gene product of 109P1 D4 set forth in Figures 2 and 3, the specific search peptides used to generate the tables are listed in Table VII.

Computer searches for epitopes bearing HLA Class I or Class 11 supermotifs or motifs are performed as follows.

All translated 109P1D4 protein sequences are analyzed using a text string search software program to identify potential peptide sequences containing appropriate HLA binding motifs ; such programs are readily produced in accordance with information in the art in view of known motif/supermotif disclosures. Furthermore, such calculations can be made mentally. identified A2-, A3-, and DR-supermotif sequences are scored using polynomial algorithms to predict their capacity to bind to specific HLA-Class I or Class II molecules. These polynomial algorithms account for the impact of different amino acids at different positions, and are essentially based on the premise that the overall affinity (or AG) of peptide-HLA molecule interactions can be approximated as a linear polynomial function of the type : "AG"= ai x a2s x a31 x an ; where agi is a coefficient which represents the effect of the presence of a given amino acid U) at a given position (i) along the sequence of a peptide of n amino acids. The crucial assumption of this method is that the effects at each position are essentially independent of each other (i. e., independent binding of individual side-chains). When residue j occurs at position i in the peptide, it is assumed to contribute a constant amount ji to the free energy of binding of the peptide irrespective of the sequence of the rest of the peptide.

The method of derivation of specific algorithm coefficients has been described in Gulukota et al., J. Mol. BioL 267 : 1258-126, 1997 ; (see also Sidney et al., Human Immunol. 45 : 79-93, 1996 ; and Southwood et al., J. Immunol. 160 : 3363- 3373, 1998). Briefly, for all i positions, anchor and non-anchor alike, the geometric mean of the average relative binding (ARB) of all peptides carrying j is calculated relative to the remainder of the group, and used as the estimate of ji. For Class "peptide6, if multiple alignments are possible, only the highest scoring alignment is utilized, following an iterative procedure.

To calculate an algorithm score of a given peptide in a test set, the ARB values corresponding to the sequence of the peptide are multiplied. If this product exceeds a chosen threshold, the peptide is predicted to bind. Appropriate thresholds are chosen as a function of the degree of stringency of prediction desired.

Selection of HLA-A2 supertype cross-reactive peptides Protein sequences from 109P1 D4 are scanned utilizing motif identification software, to identify 8-, 9-10-and 11- mer sequences containing the HLA-A2-supermotif main anchor specificity. Typically, these sequences are then scored using the protocol described above and the peptides corresponding to the positive-scoring sequences are synthesized and tested for their capacity to bind purified HLA-A*0201 molecules in vitro (HLA-A*0201 is considered a prototype A2 supertype molecule).

These peptides are then tested for the capacity to bind to additional A2-supertype molecules (A*0202, A*0203, A*0206, and A*6802). Peptides that bind to at least three of the five A2-supertype alleles tested are typically deemed A2- supertype cross-reactive binders. Preferred peptides bind at an affinity equal to or less than 500 nM to three or more HLA- A2 supertype molecules.

Selection of HLA-A3 supermotif-bearing epitopes The 109P1 D4 protein sequence (s) scanned above is also examined for the presence of peptides with the HLA-A3- supermotif primary anchors. Peptides corresponding to the HLA A3 supermotif-bearing sequences are then synthesized and tested for binding to HLA-A*0301 and HLA-A*1101 molecules, the molecules encoded by the two most prevalent A3- supertype alleles. The peptides that bind at least one of the two alleles with binding affinities of <500 nM, often zu 200 nM, are then tested for binding cross-reactivity to the other common A3-supertype alieles (e. g., A*3101, A*3301, and A*6801) to identify those that can bind at least three of the five HLA-A3-supertype molecules tested.

Selection of HLA-B7 supermotif bearing epitopes The 109P1 D4 protein (s) scanned above is also analyzed for the presence of 8-, 9-10-, or 11-mer peptides with the HLA-B7-supermotif. Corresponding peptides are synthesized and tested for binding to HLA-B*0702, the molecule encoded by the most common B7-supertype allele (i. e., the prototype B7 supertype allele). Peptides binding B*0702 with ICso of <500 nM are identified using standard methods. These peptides are then tested for binding to other common B7-supertype molecules (e. g., B*3501, B*5101, B*5301, and B*5401). Peptides capable of binding to three or more of the five B7- supertype alleles tested are thereby identified.

Selection of A1 and A24 motif-bearing epitopes To further increase population coverage, HLA-A1 and-A24 epitopes can also be incorporated into vaccine compositions. An analysis of the 109P1D4 protein can also be performed to identify HLA-A1-and A24-motif-containing sequences.

High affinity and/or cross-reactive binding epitopes that bear other motif and/or supermotifs are identified using analogous methodology.

Example 14 : Confirmation of Immunogenicity Cross-reactive candidate CTL A2-supermotif-bearing peptides that are identified as described herein are selected to confirm in vitro immunogenicity. Confirmation is performed using the following methodology : Target Cell Lines for Cellular Screening : The. 221A2. 1 cell line, produced by transferring the HLA-A2. 1 gene into the HLA-A,-B,-C null mutant human B- lymphoblastoid cell line 721. 221, is used as the peptide-loaded target to measure activity of HLA-A2. 1-restricted CTL. This cell line is grown in RPMI-1640 medium supplemented with antibiotics, sodium pyruvate, nonessential amino acids and 10% (v/v) heat inactivated FCS. Cells that express an antigen of interest, or transfectants comprising the gene encoding the antigen of interest, can be used as target cells to confirm the ability of peptide-specific CTLs to recognize endogenous antigen.

Primary CTL induction Cultures : Generation of Dendritic Cells (DC) : PBMCs are thawed in RPMI with 30 g/mi DNAse, washed twice and resuspended in complete medium (RPMI-1640 plus 5% AB human serum, non-essential amino acids, sodium pyruvate, L- glutamin and penicillin/streptomycin). The monocytes are purified by plating 10 x 106 PBMC/well in a 6-well plate. After 2 hours at 37°C, the non-adherent cells are removed by gently shaking the plates and aspirating the supernatants. The wells are washed a total of three times with 3 ml RPMI to remove most of the non-adherent and loosely adherent cells. Three mi of complete medium containing 50 ng/ml of GM-CSF and 1, 000 U/ml of IL-4 are then added to each Well. TNFa is added to the DCs on day 6 at 75 ng/mi and the cells are used for CTL induction cultures on day 7.

Induction of CTL with DC and Peptide : CD8* T-cells are isolated by positive selection with Dynal immunomagnetic beads (Dynabeads0 M-450) and the detacha-bead0 reagent. Typically about 200-250x106 PBMC are processed to obtain 24x106 CD8+ T-cells (enough for a 48-well plate culture). Briefly, the PBMCs are thawed in RPMI with 30pg/ml DNAse, washed once with PBS containing 1% human AB serum and resuspended in PBS/1% AB serum at a concentration of 20x106cellslml. The magnetic beads are washed 3 times with PBS/AB serum, added to the cells (140pl beads/20xl 06 cells) and incubated for 1 hour at 4°C with continuous mixing. The beads and cells are washed 4x with PBS/AB serum to remove the nonadherent cells and resuspended at 100x106 cells/ml (based on the original cell number) in PBS/AB serum containing 100) Ji/mi detacha-bead@ reagent and 30 µg/ml DNAse. The mixture is incubated for 1 hour at room temperature with continuous mixing. The beads are washed again with PBS/AB/DNAse to collect the CD8+ T-cells. The DC are collected and centrifuged at 1300 rpm for 5-7 minutes, washed once with PBS with 1% BSA, counted and pulsed with 40pglml of peptide at a cell concentration of 1-2x106/m1 in the presence of 3pg/ml R2-microglobulin for 4 hours at 20°C. The DC are then irradiated (4, 200 rads), washed 1 time with medium and counted again.

Setting up induction cultures : 0. 25 ml cytokine-generated DC (at 1x105 cells/ml) are co-cultured with 0. 25m, of CD8+ T-cells (at 2x106 cell/ml) in each well of a 48-well plate in the presence of 10 ng/ml of IL-7. Recombinant human L-10 is added the next day at a final concentration of 10 ng/ml and rhuman IL-2 is added 48 hours later at 10 IU/ml.

Restimulation of the induction cultures with peptide-pulsed adherent cells : Seven and fourteen days after the primary induction, the cells are restimulated with peptide-puised adherent cells. The PBMCs are thawed and washed twice with RPMI and DNAse. The cells are resuspended at 5x106 cells/ml and irradiated at ~4200 rads. The PBMCs are plated at 2x106 in 0. 5 ml complete medium per well and incubated for 2 hours at 37°C. The plates are washed twice with RPMI by tapping the plate gently to remove the nonadherent cells and the adherent cells pulsed with 10Nglml of peptide in the presence of 3 pg/m, ß2 microg, obu, in in 0. 25m, RPMI/5% AB per well for 2 hours at 37°C. Peptide solution from each well is aspirated and the wells are washed once with RPMI. Most of the media is aspirated from the induction cultures (CD8+ cells) and brought to 0. 5 ml with fresh media. The cells are then transferred to the wells containing the peptide-pulsed adherent cells. Twenty four hours later recombinant human IL-10 is added at a final concentration of 10 ng/ml and recombinant human IL2 is added the next day and again 2-3 days later at 501U/ml (Tsai et al., Critical Reviews in Immunology 18 (1-2) : 65-75, 1998). Seven days later, the cultures are assayed for CTL activity in a 5lCr release assay, in some experiments the cultures are assayed for peptide-specific recognition in the in situ IFNy ELISA at the time of the second restimulation followed by assay of endogenous recognition 7 days later. After expansion, activity is measured in both assays for a side-by-side comparison.

Measurement of CTL lytic activity by 51Cr release.

Seven days after the second restimulation, cytotoxicity is determined in a standard (5 hr) 5'Cr release assay by assaying individual wells at a single E : T. Peptide-pulsed targets are prepared by incubating the cells with lOpg/mi peptide overnight at 37°C.

Adherent target cells are removed from culture flasks with trypsin-EDTA. Target cells are labeled with 200pCi of 51Cr sodium chromate (Dupont, Wilmington, DE) for 1 hour at 37°C. Labeled target cells are resuspended at 106 per ml and diluted 1 : 10 with K562 cells at a concentration of 3. 3x106/ml (an NK-sensitive erythroblastoma cell line used to reduce non- specific lysis). Target cells (100 pu) and effectors (100NI) are plated in 96 well round-bottom plates and incubated for 5 hours at 37°C. At that time, 100 pi of supernatant are collected from each well and percent lysis is determined according to the formula : [ (cpm of the test sample-cpm of the spontaneous 51Cr release sample)/ (cpm of the maximal 51Cr release sample- cpm of the spontaneous 5aCr release sample)] x 100.

Maximum and spontaneous release are determined by incubating the labeled targets with 1% Triton X-100 and media alone, respectively. A positive culture is defined as one in which the specific lysis (sample-background) is 10% or higher in the case of individual wells and is 15% or more at the two highest E : T ratios when expanded cultures are assayed.

In situ Measurement of Human IFNY Production as an indicator of Peptide-specific and Endogenous Recognition Immulon 2 plates are coated with mouse anti-human FNy monoclonal antibody (4 K^g/m, 0. 1M NaHCO3, pH8. 2) overnight at 4°C. The plates are washed with Ca2+, Mg2+-free PBS/0. 05% Tween 20 and blocked with PBS/10% FCS for two hours, after which the CTLs (100 Ilwell) and targets (100 Il,/we") are added to each well, leaving empty wells for the standards and blanks (which received media only). The target cells, either peptide-pulsed or endogenous targets, are used at a concentration of 1 x106 ce"s/m,. The plates are incubated for 48 hours at 37°C with 5% CO2.

Recombinant human IFN-gamma is added to the standard wells starting at 400 pg or 1200pg/100 microliter/well and the plate incubated for two hours at 37°C. The plates are washed and 100 jl, of biotinylated mouse anti-human IFN- gamma monoclonal antibody (2 microgram/ml in PBS/3% FCS/0. 05% Tween 20) are added and incubated for 2 hours at room temperature. After washing again, 100 microliter HRP-streptavidin (1 : 4000) are added and the plates incubated for one hour at room temperature. The plates are then washed 6x with wash buffer, 100 microliter/well developing solution (TMB 1 : 1) are added, and the plates allowed to develop for 5-15 minutes. The reaction is stopped with 50 micro, 1M H3P04 and read at OD450. A culture is considered positive if it measured at least 50 pg of IFN-gamma/well above background and is twice the background level of expression.

CTL Expansion.

Those cultures that demonstrate specific lytic activity against peptide-pulsed targets and/or tumor targets are expanded over a two week period with anti-CD3. Briefly, 5x104 CD8+ cells are added to a T25 flask containing the following : 1x106 irradiated (4, 200 rad) PBMC (autologous or allogeneic) per ml, 2x105 irradiated (8, 000 rad) EBV-transformed cells per ml, and OKT3 (anti-CD3) at 30ng per ml in RPMI-1640 containing 10% (v/v) human AB serum, non-essential amino acids, sodium pyruvate, 25pM 2-mercaptoethanol, L-glutamine and penicillin/streptomycin. Recombinant human IL2 is added 24 hours later at a final concentration of 200tU/m ! and every three days thereafter with fresh media at 50, Ulml. The cells are split if the cell concentration exceeds 1x106/m, and the cultures are assayed between days 13 and 15 at E : T ratios of 30, 10, 3 and 1 : 1 in the 51Cr release assay or at 1x106/ml in the in situ FNy assay using the same targets as before the expansion.

Cultures are expanded in the absence of anti-CD3+ as follows. Those cultures that demonstrate specific lytic activity against peptide and endogenous targets are selected and 5x104 CD8+ cells are added to a T25 flask containing the following : 1x106 autologous PBMC per ml which have been peptide-pulsed with 10 jj. g/mi peptide for two hours at 37°C and irradiated (4, 200 rad) ; 2x105 irradiated (8, 000 rad) EBV-transformed cells per mi RPMI-1640 containing 10% (v/v) human AB serum, non-essential AA, sodium pyruvate, 25mM 2-ME, L-glutamine and gentamicin.

Immunogenicity of A2 supermotif-bearing peptides A2-supermotif cross-reactive binding peptides are tested in the cellular assay for the ability to induce peptide- specific CTL in normal individuals. In this analysis, a peptide is typically considered to be an epitope if it induces peptide- specific CTLs in at least individuals, and preferably, also recognizes the endogenously expressed peptide.

Immunogenicity can also be confirmed using PBMCs isolated from patients bearing a tumor that expresses 109P1D4. Briefly, PBMCs are isolated from patients, re-stimulated with peptide-pulsed monocytes and assayed for the ability to recognize peptide-pulsed target cells as well as transfected cells endogenous, y expressing the antigen.

Evaluation of A*031A11 immunogenicity HLA-A3 supermotif-bearing cross-reactive binding peptides are also evaluated for immunogenicity using methodology analogous for that used to evaluate the immunogenicity of the HLA-A2 supermotif peptides.

Evaluation of B7 immunogenicity Immunogenicity screening of the B7-supertype cross-reactive binding peptides identified as set forth herein are confirmed in a manner analogous to the confirmation of A2-and A3-supermotif-bearing peptides.

Peptides bearing other supermotifs/motifs, e. g., HLA-A1, HLA-A24 etc. are also confirmed using similar methodology Example 15 : Implementation of the Extended Supermotif to Improve the Binding Capacity of Native Epitopes by Creating Analogs HLA motifs and supermotifs (comprising primary and/or secondary residues) are useful in the identification and preparation of highly cross-reactive native peptides, as demonstrated herein. Moreover, the definition of HLA motifs and supermotifs also allows one to engineer highly cross-reactive epitopes by identifying residues within a native peptide sequence which can be analoge to confer upon the peptide certain characteristics, e. g. greater cross-reactivity within the group of HLA molecules that comprise a supertype, and/or greater binding affinity for some or all of those HLA molecules.

Examples of analoging peptides to exhibit modulated binding affinity are set forth in this example.

Analoqing at Primary Anchor Residues Peptide engineering strategies are implemented to further increase the cross-reactivity of the epitopes. For example, the main anchors of A2-supermotif-bearing peptides are altered, for example, to introduce a preferred L, !, V, or M at position 2, and I or V at the C-terminus.

To analyze the cross-reactivity of the analog peptides, each engineered analog is initially tested for binding to the prototype A2 supertype allele A*0201, then, if A*0201 binding capacity is maintained, for A2-supertype cross-reactivity.

Alternatively, a peptide is confirmed as binding one or all supertype members and then analoge to modulate binding affinity to any one (or more) of the supertype members to add population coverage.

The selection of analogs for immunogenicity in a cellular screening analysis is typically further restricted by the capacity of the parent wild type (WT) peptide to bind at least weakly, i. e., bind at an ICso of 5000nM or less, to three of more A2 supertype alleles. The rationale for this requirement is that the WT peptides must be present endogenous, y in sufficient quantity to be biologically relevant. Analoged peptides have been shown to have increased immunogenicity and cross- reactivity by T cells specific for the parent epitope (see, e. g., Parkhurst et al., J. Immunol. 157 : 2539, 1996 ; and Pogue et al., Proc. Natl. Acad. Sci. USA 92 : 8166, 1995).

In the cellular screening of these peptide analogs, it is important to confirm that analog-specific CTLs are also able to recognize the wild-type peptide and, when possible, target cells that endogenously express the epitope.

Analoging of HLA-A3 and B7-supermotif-bearing peptides Analogs of HLA-A3 supermotif-bearing epitopes are generated using strategies similar to those employed in analoging HLA-A2 supermotif-bearing peptides. For example, peptides binding to 3/5 of the A3-supertype molecules are engineered at primary anchor residues to possess a preferred residue (V, S, M, or A) at position 2.

The analog peptides are then tested for the ability to bind A*03 and A*11 (prototype A3 supertype alleles). Those peptides that demonstrate < 500 nM binding capacity are then confirmed as having A3-supertype cross-reactivity.

Similarly to the A2-and A3-motif bearing peptides, peptides binding 3 or more B7-supertype alleles can be improved, where possible, to achieve increased cross-reactive binding or greater binding affinity or binding half life. B7 supermotif-bearing peptides are, for example, engineered to possess a preferred residue (V, 1, L, or F) at the C-terminal primary anchor position, as demonstrated by Sidney et al. (J. Immunol. 157 : 3480-3490, 1996).

Analoging at primary anchor residues of other motif and/or supermotif-bearing epitopes is performed in a like manner.

The analog peptides are then be confirmed for immunogenicity, typically in a cellular screening assay. Again, it is generally important to demonstrate that analog-specific CTLs are also able to recognize the wild-type peptide and, when possible, targets that endogenous, y express the epitope.

Analoging at Secondary Anchor Residues Moreover, HLA supermotifs are of value in engineering highly cross-reactive peptides and/or peptides that bind HLA molecules with increased affinity by identifying particular residues at secondary anchor positions that are associated with such properties. For example, the binding capacity of a B7 supermotif-bearing peptide with an F residue at position 1 is analyzed. The peptide is then analoge to, for example, substitute L for F at position 1. The analoge peptide is evaluated for increased binding affinity, binding half life and/or increased cross-reactivity. Such a procedure identifies analoge peptides with enhanced properties.

Engineered analogs with sufficiently improved binding capacity or cross-reactivity can also be tested for immunogenicity in HLA-B7-transgenic mice, following for example, IFA immunization or lipopeptide immunization. Analoge peptides are additional tested for the ability to stimulate a recall response using PBMC from patients with 109P1 D4- expressing tumors.

Other analoging strategies Another form of peptide analoging, unrelated to anchor positions, involves the substitution of a cysteine with a- amino butyric acid. Due to its chemical nature, cysteine has the propensity to form disulfide bridges and sufficiently alter the peptide structural so as to reduce binding capacity. Substitution of a-amino butyric acid for cysteine not only alleviates this problem, but has been shown to improve binding and crossbinding capabilities in some instances (see, e. g., the review by Sette et al., In : Persistent Viral Infections, Eds. R. Ahmed and I. Chen, John Wiley & Sons, England, 1999).

Thus, by the use of single amino acid substitutions, the binding properties and/or cross-reactivity of peptide ligands for HLA supertype molecules can be modulated.

Example 16 : Identification and confirmation of 109P1 D4-derived sequences with HLA-DR binding motifs Peptide epitopes bearing an HLA class II supermotif or motif are identified and confirmed as outlined below using methodology similar to that described for HLA Class I peptides.

Selection of HLA-DR-supermotif-bearing epitopes.

To identify 109P1 D4-derived, HLA c, ass"HTL epitopes, a 1 09P1 D4 antigen is analyzed for the presence of sequences bearing an HLA-DR-motif or supermotif. Specifically, 15-mer sequences are selected comprising a DR- supermotif, comprising a 9-mer core, and three-residue N-and C-terminal flanking regions (15 amino acids total).

Protocols for predicting peptide binding to DR molecules have been developed (Southwood et al., J. Immunol.

160 : 3363-3373, 1998). These protocols, specific for individual DR molecules, allow the scoring, and ranking, of 9-mer core regions. Each protocol not only scores peptide sequences for the presence of DR-supermotif primary anchors (i. e., at position 1 and position 6) within a 9-mer core, but additional evaluates sequences for the presence of secondary anchors.

Using aliele-specific selection tables (see, e. g., Southwood et al., ibid.), it has been found that these protocols efficiently select peptide sequences with a high probability of binding a particular DR molecule. Additionally, it has been found that performing these protocols in tandem, specifically those for DR1, DR4w4, and DR7, can efficiently select DR cross-reactive peptides.

The 109P1D4-derived peptides identified above are tested for their binding capacity for various common HLA-DR molecules. All peptides are initially tested for binding to the DR molecules in the primary panel : DR1, DR4w4, and DR7.

Peptides binding at least two of these three DR molecules are then tested for binding to DR2w2 pl, DR2w2 82, DR6w19, and DR9 molecules in secondary assays. Finally, peptides binding at least two of the four secondary panel DR molecules, and thus cumulatively at least four of seven different DR molecules, are screened for binding to DR4w15, DR5w11, and DR8w2 molecules in tertiary assays. Peptides binding at least seven of the ten DR molecules comprising the primary, secondary, and tertiary screening assays are considered cross-reactive DR binders. 109P1 D4-derived peptides found to bind common HLA-DR alleles are of particular interest.

Selection of DR3 motif peptides Because HLA-DR3 is an allele that is prevalent in Caucasian, Black, and Hispanic populations, DR3 binding capacity is a relevant criterion in the selection of HTL epitopes. Thus, peptides shown to be candidates may also be assayed for their DR3 binding capacity. However, in view of the binding specificity of the DR3 motif, peptides binding only to DR3 can also be considered as candidates for inclusion in a vaccine formulation.

To efficiently identify peptides that bind DR3, target 109P1D4 antigens are analyzed for sequences carrying one of the two DR3-specific binding motifs reported by Geluk et al. (J. Immunol. 152 : 5742-5748, 1994). The corresponding peptides are then synthesized and confirmed as having the ability to bind DR3 with an affinity of 1 j. tu or better, i. e., less than 1 jj. M. Peptides are found that meet this binding criterion and qualify as HLA class 1I high affinity binders.

DR3 binding epitopes identified in this manner are included in vaccine compositions with DR supermotif-bearing peptide epitopes.

Similarly to the case of HLA class 1 motif-bearing peptides, the class II motif-bearing peptides are analoge to improve affinity or cross-reactivity. For example, aspartic acid at position 4 of the 9-mer core sequence is an optimal residue for DR3 binding, and substitution for that residue often improves DR 3 binding.

Example 17 : Immunogenicity of 109P1D4-derived HTL epitopes This example determines immunogenic DR supermotif-and DR3 motif-bearing epitopes among those identified using the methodology set forth herein.

Immunogenicity of HTL epitopes are confirmed in a manner analogous to the determination of immunogenicity of CTL epitopes, by assessing the ability to stimulate HTL responses and/or by using appropriate transgenic mouse models.

Immunogenicity is determined by screening for : 1.) in vitro primary induction using normal PBMC or 2.) recall responses from patients who have 109P1D4-expressing tumors.

Example 18 : Calculation of phenotypic frequencies of HLA supertypes in various ethnic backgrounds to determine breadth of population coverage This example illustrates the assessment of the breadth of population coverage of a vaccine composition comprised of multiple epitopes comprising multiple supermotifs and/or motifs.

In order to analyze population coverage, gene frequencies of HLA alleles are determined. Gene frequencies for each HLA ai ! eie are calculated from antigen or allele frequencies utilizing the binomial distribution formulae gf=1- (SQRT (1- af)) (see, e. g., Sidney et al., Human Immunol. 45 : 79-93, 1996). To obtain overall phenotypic frequencies, cumulative gene frequencies are calculated, and the cumulative antigen frequencies derived by the use of the inverse formula [af=l- (l-Cg2].

Where frequency data is not available at the level of DNA typing, correspondence to the serologically defined antigen frequencies is assumed. To obtain total potential supertype population coverage no linkage disequilibrium is assumed, and only alieles confirmed to belong to each of the supertypes are included (minimal estimates). Estimates of total potential coverage achieved by inter-loci combinations are made by adding to the A coverage the proportion of the non-A covered population that could be expected to be covered by the B alleles considered (e. g., total=A+B* (1-A)). Confirmed members of the A3-like supertype are A3, A11, A31, A*3301, and A*6801. Although the A3-like supertype may also include A34, A66, and A*7401, these alieles were not included in overall frequency calculations. Likewise, confirmed members of the A2-like supertype family are A*0201, A*0202, A*0203, A*0204, A*0205, A*0206, A*0207, A*6802, and A*6901. Finally, the B7-like supertype-confirmed alleles are : B7, B*3501-03, B51, B*5301, B*5401, B*5501-2, B*5601, B*6701, and B*7801 (potentially also B*1401, B*3504-06, B*4201, and B*5602).

Population coverage achieved by combining the A2-, A3-and B7-supertypes is approximately 86% in five major ethnic groups. Coverage may be extended by including peptides bearing the A1 and A24 motifs. On average, A1 is present in 12% and A24 in 29% of the population across five different major ethnic groups (Caucasian, North American Black, Chinese, Japanese, and Hispanic). Together, these alleles are represented with an average frequency of 39% in these same ethnic populations. The total coverage across the major ethnicities when A1 and A24 are combined with the coverage of the A2-, A3-and B7-supertype alleles is >95%, see, e. g., Table IV (G). An analogous approach can be used to estimate population coverage achieved with combinations of class II motif-bearing epitopes.

Immunogenicity studies in humans (e. g., Bertoni et al., J. Clin. Invest. 100 : 503, 1997 ; Doolan et al., Immunity7 : 97, 1997 ; and Threlkeld et al., J. Immunol. 159 : 1648, 1997) have shown that highly cross-reactive binding peptides are almost always recognized as epitopes. The use of highly cross-reactive binding peptides is an important selection criterion in identifying candidate epitopes for inclusion in a vaccine that is immunogenic in a diverse population.

With a sufficient number of epitopes (as disclosed herein and from the art), an average population coverage is predicted to be greater than 95% in each of five major ethnic populations. The game theory Monte Carlo simulation analysis, which is known in the art (see e. g., Osborne, M. J. and Rubinstein, A."A course in game theory"MIT Press, 1994), can be used to estimate what percentage of the individuals in a population comprised of the Caucasian, North American Black, Japanese, Chinese, and Hispanic ethnic groups would recognize the vaccine epitopes described herein. A preferred percentage is 90%. A more preferred percentage is 95%.

Example 19 : CTL Recognition Of Endogenously Processed Antigens After Priming This example confirms that CTL induced by native or analoge peptide epitopes identified and selected as described herein recognize endogenous, y synthesized, i. e., native antigens.

Effector cells isolated from transgenic mice that are immunized with peptide epitopes, for example HLA-A2 supermotif-bearing epitopes, are re-stimulated in vitro using peptide-coated stimulator cells. Six days later, effector cells are assayed for cytotoxicity and the cell lines that contain peptide-specific cytotoxic activity are further re-stimulated. An additional six days later, these cell lines are tested for cytotoxic activity on sCr labeled Jurkat-A2. 1/Kb target cells in the absence or presence of peptide, and also tested on sCr labeled target cells bearing the endogenous, y synthesized antigen, Le. cells that are stably transfected with 109P1D4 expression vectors.

The results demonstrate that CTL lines obtained from animals primed with peptide epitope recognize endogenous, y synthesized 109P1 D4 antigen. The choice of transgenic mouse model to be used for such an analysis depends upon the epitope (s) that are being evaluated. In addition to HLA-A*0201/Kb transgenic mice, several other transgenic mouse models including mice with human A11, which may also be used to evaluate A3 epitopes, and B7 alleles have been characterized and others (e. g., transgenic mice for HLA-A1 and A24) are being developed. HLA-DR1 and HLA- DR3 mouse models have also been developed, which may be used to evaluate HTL epitopes.

Example 20 : Activity Of CTL-HTL Conjugated Epitopes In Transgenic Mice This example illustrates the induction of CTLs and HTLs in transgenic mice, by use of a 109P1 D4-derived CTL and HTL peptide vaccine compositions. The vaccine composition used herein comprise peptides to be administered to a patient with a 109P1D4-expressing tumor. The peptide composition can comprise multiple CTL and/or HTL epitopes. The epitopes are identified using methodology as described herein. This example also illustrates that enhanced immunogenicity can be achieved by inclusion of one or more HTL epitopes in a CTL vaccine composition ; such a peptide composition can comprise an HTL epitope conjugated to a CTL epitope. The CTL epitope can be one that binds to multiple HLA family members at an affinity of 500 nM or less, or analogs of that epitope. The peptides may be lipidated, if desired.

Immunization procedures ; Immunization of transgenic mice is performed as described (Alexander et aL, J.

Immunol. 159 : 4753-4761, 1997). For example, A2/Kb mice, which are transgenic for the human HLA A2. 1 allele and are used to confirm the immunogenicity of HLA-A*0201 motif-or HLA-A2 supermotif-bearing epitopes, and are primed subcutaneously (base of the tail) with a 0. 1 ml of peptide in Incomplete Freund's Adjuvant, or if the peptide composition is a lipidated CTL/HTL conjugate, in DMSO/saline, or if the peptide composition is a polypeptide, in PBS or Incomplete Freund's Adjuvant. Seven days after priming, splenocytes obtained from these animals are restimulated with syngenic irradiated LPS- activated lymphoblasts coated with peptide.

Cell lines : Target cells for peptide-specific cytotoxicity assays are Jurkat cells transfected with the HLA-A2. 1/Kb chimeric gene (e. g., Vitiello et al., J. Exp. Med. 173 : 1007, 1991) In vitro CTL activation : One week after priming, spleen cells (30x106 cells/flask) are co-cultured at 37°C with syngeneic, irradiated (3000 rads), peptide coated lymphoblasts (10x106 cellslflask) in 10 ml of culture medium25 flask.

After six days, effector cells are harvested and assayed for cytotoxic activity.

Assay for cytotoxic activity : Target cells (1. 0 to 1. 5x106) are incubated at 37°C in the presence of 200 nui of 51Cr.

After 60 minutes, cells are washed three times and resuspended in RIO medium. Peptide is added where required at a concentration of 1 pg/ml. For the assay, 104 51Cr-labeled target cells are added to different concentrations of effector cells (final volume of 200 pI) in U-bottom 96-well plates. After a six hour incubation period at 37°C, a 0. 1 ml aliquot of supernatant is removed from each well and radioactivity is determined in a Micromedic automatic gamma counter. The percent specific lysis is determined by the formula : percent specific release = 100 x (experimental release-spontaneous release)/ (maximum release-spontaneous release). To facilitate comparison between separate CTL assays run under the same conditions, % 51Cr release data is expressed as lytic units/106 cells. One lytic unit is arbitrarily defined as the number of effector cells required to achieve 30% lysis of 10, 000 target cells in a six hour 51Cr release assay. To obtain specific lytic unitsI106, the lytic units/I 06 obtained in the absence of peptide is subtracted from the lytic units/10 obtained in the presence of peptide. For example, if 30% 51Cr release is obtained at the effector (E) : target (T) ratio of 50 : 1 (i. e., 5x105 effector cells for 10, 000 targets) in the absence of peptide and 5 : 1 (i. e., 5x104 effector cells for 10, 000 targets) in the presence of peptide, the specific ytic units would be : [ (1/50, 000)- (1/500, 000)] x 106 = 18 LU.

The results are analyzed to assess the magnitude of the CTL responses of animals injected with the immunogenic CTL/HTL conjugate vaccine preparation and are compared to the magnitude of the CTL response achieved using, for example, CTL epitopes as outlined above in the Example entitled"Confirmation of Immunogenicity."Analyses similar to this may be performed to confirm the immunogenicity of peptide conjugates containing multiple CTL epitopes and/or multiple HTL epitopes. In accordance with these procedures, it is found that a CTL response is induced, and concomitantly that an HTL response is induced upon administration of such compositions.

Example 21 : Selection of CTL and HTL epitopes for inclusion in a 109P1D4specific vaccine.

This example illustrates a procedure for selecting peptide epitopes for vaccine compositions of the invention. The peptides in the composition can be in the form of a nucleic acid sequence, either single or one or more sequences (i.e., minigene) that encodes peptide (s), or can be single and/or polyepitopic peptides.

The following principles are utilized when selecting a plurality of epitopes for inclusion in a vaccine composition.

Each of the following principles is balanced in order to make the selection, Epitopes are selected which, upon administration, mimic immune responses that are correlated with 109P1 D4 clearance. The number of epitopes used depends on observations of patients who spontaneously clear 109P1 D4. For example, if it has been observed that patients who spontaneously clear 109P1D4-expressing cells generate an immune response to at least three (3) epitopes from 109P1 D4 antigen, then at least three epitopes should be included for HLA class 1. A similar rationale is used to determine HLA class 11 epitopes.

Epitopes are often selected that have a binding affinity of an IC5o of 500 nM or less for an HLA class 1 molucule, or for class ass", an ICso of 1000 nM or less ; or HLA Class I peptides with high binding scores from the BIMAS web site, at URL bimas. dcrt. nih, gov/.

In order to achieve broad coverage of the vaccine through out a diverse population, sufficient supermotif bearing peptides, or a sufficient array of allele-specific motif bearing peptides, are selected to give broad population coverage. In one embodiment, epitopes are selected to provide at least 80% population coverage. A Monte Carlo analysis, a statistical evaluation known in the art, can be employed to assess breadth, or redundancy, of population coverage.

When creating polyepitopic compositions, or a minigene that encodes same, it is typically desirable to generate the smallest peptide possible that encompasses the epitopes of interest. The principles employed are similar, if not the same, as those employed when selecting a peptide comprising nested epitopes. For example, a protein sequence for the vaccine composition is selected because it has maximal number of epitopes contained within the sequence, i.e., it has a high concentration of epitopes. Epitopes may be nested or overlapping (ive., frame shifted relative to one another). For example, with overlapping epitopes, two 9-mer epitopes and one 10-mer epitope can be present in a 10 amino acid peptide. Each epitope can be exposed and bound by an HLA molecule upon administration of such a peptide. A multi-epitopic, peptide can be generated synthetically, recombinantly, or via cleavage from the native source. Alternatively, an analog can be made of this native sequence, whereby one or more of the epitopes comprise substitutions that alter the cross-reactivity and/or binding affinity properties of the polyepitopic peptide. Such a vaccine composition is administered for therapeutic or prophylactic purposes. This embodiment provides for the possibility that an as yet undiscovered aspect of immune system processing will apply to the native nested sequence and thereby facilitate the production of therapeutic or prophylactic immune response-inducing vaccine compositions. Additionally such an embodiment provides for the possibility of motif- bearing epitopes for an HLA makeup that is presently unknown. Furthermore, this embodiment (absent the creating of any analogs) directs the immune response to multiple peptide sequences that are actually present in 109P1 D4, thus avoiding the need to evaluate any junctional epitopes. Lastly, the embodiment provides an economy of scale when producing nucleic acid vaccine compositions. Related to this embodiment, computer programs can be derived in accordance with principles in the art, which identify in a target sequence, the greatest number of epitopes per sequence length.

A vaccine composition comprised of selected peptides, when administered, is safe, efficacious, and elicits an immune response similar in magnitude to an immune response that controls or clears cells that bear or overexpress 109P1 D4.

Example 22 : Construction of"Minigene"Multi-Epitope DNA Plasmids This example discusses the construction of a minigene expression plasmid. Minigene plasmids may, of course, contain various configurations of B cell, CTL and/or HTL epitopes or epitope analogs as described herein.

A minigene expression plasmid typically includes multiple CTL and HTL peptide epitopes. In the present example, HLA-A2,-A3,-B7 supermotif-bearing peptide epitopes and HLA-A1 and-A24 motif-bearing peptide epitopes are used in conjunction with DR supermotif-bearing epitopes and/or DR3 epitopes. HLA class 1 supermotif or motif-bearing peptide epitopes derived 109P1D4, are selected such that multiple supermotifs/motifs are represented to ensure broad population coverage. Similarly, HLA clashs il epitopes are selected from 109P1D4 to provide broad population coverage, ive. both HLA DR-1-4-7 supermotif-bearing epitopes and HLA DR-3 motif-bearing epitopes are selected for inclusion in the minigene construct. The selected CTL and HTL epitopes are then incorporated into a minigene for expression in an expression vector.

Such a construct may additionally include sequences that direct the HTL epitopes to the endoplasmic reticulum.

For example, the li protein may be fused to one or more HTL epitopes as described in the art, wherein the CLIP sequence of the li protein is removed and replaced with an HLA clashs il epitope sequence so that HLA clashs il epitope is directed to the endoplasmic reticulum, where the epitope binds to an HLA clashs il molecules.

This example illustrates the methods to be used for construction of a minigene-bearing expression plasmid. Other expression vectors that may be used for minigene compositions are available and known to those of skill in the art.

The minigene DNA plasmid of this example contains a consensus Kozak sequence and a consensus murine kappa Ig-light chain signal sequence followed by CTL and/or HTL epitopes selected in accordance with principles disclosed herein. The sequence encodes an open reading frame fused to the Myc and His antibody epitope tag coded for by the pcDNA 3. 1 Myc-His vector.

Overlapping oligonucleotides that can, for example, average about 70 nucleotides in length with 15 nucleotide overlaps, are synthesized and HPLC-purified. The oligonucleotides encode the selected peptide epitopes as well as appropriate linker nucleotides, Kozak sequence, and signal sequence. The final multiepitope minigene is assembled by extending the overlapping oligonucleotides in three sets of reactions using PCR. A Perkin/Elmer 9600 PCR machine is used and a total of 30 cycles are performed using the following conditions : 95°C for 15 sec, annealing temperature (5'below the lowest calculated Tm of each primer pair) for 30 sec, and 72°C for 1 min.

For example, a minigene is prepared as follows. For a first PCR reaction, 5 S of each of two oligonucleotides are annealed and extended : In an example using eight oligonucleotides, i. e., four pairs of primers, oligonucleotides 1+2, 3+4, 5+6, and 7+8 are combined in 100 RI reactions containing Pfu polymerase buffer (1x= 10 mM KCL, 10 mM (NH4) 2SO4, 20 mM Tris-chloride, pH 8. 75, 2 mM MgSO4, 0. 1% Triton X-100, 100 lig/ml BSA), 0. 25 mM each dNTP, and 2. 5 U of Pfu polymerase. The full-length dimer products are gel-purified, and two reactions containing the product of 1+2 and 3+4, and the product of 5+6 and 7+8 are mixed, annealed, and extended for 10 cycles. Half of the two reactions are then mixed, and 5 cycles of annealing and extension carried out before flanking primers are added to amplify the full length product. The full- length product is gel-purified and cloned into pCR-blunt (Invitrogen) and individual clones are screened by sequencing.

Example 23 : The Plasmid Construct and the Degree to Which It Induces Immunogenicity.

The degree to which a plasmid construct, for example a plasmid constructed in accordance with the previous Example, is able to induce immunogenicity is confirmed in vitro by determining epitope presentation by APC following transduction or transfection of the APC with an epitope-expressing nucleic acid construct. Such a study determines "antigenicity"and allows the use of human APC. The assay determines the ability of the epitope to be presented by the APC in a context that is recognized by a T cell by quantifying the density of epitope-HLA class I complexes on the cell surface.

Quantitation can be performed by directly measuring the amount of peptide eluted from the APC (see, e. g., Sijts et al., J.

Immunol. 156 : 683-692, 1996 ; Demotz et al., Nature 342 : 682-684, 1989) ; or the number of peptide-HLA class I complexes can be estimated by measuring the amount of lysis or lymphokine release induced by diseased or transfected target cells, and then determining the concentration of peptide necessary to obtain equivalent levels of lysis or lymphokine release (see, e. g., Kageyama et al., J. Immunol. 154 : 567-576, 1995).

Alternatively, immunogenicity is confirmed through in vivo injections into mice and subsequent in vitro assessment of CTL and HTL activity, which are analyzed using cytotoxicity and proliferation assays, respectively, as detailed e. g., in Alexander et al., Immunity 1 : 751-761, 1994.

For example, to confirm the capacity of a DNA minigene construct containing at least one HLA-A2 supermotif peptide to induce CTLs in vivo, HLA-A2. 1/Kb transgenic mice, for example, are immunized intramuscularly with 100 zu of naked cDNA. As a means of comparing the level of CTLs induced by cDNA immunization, a control group of animals is also immunized with an actual peptide composition that comprises multiple epitopes synthesized as a single polypeptide as they would be encoded by the minigene.

Splenocytes from immunized animals are stimulated twice with each of the respective compositions (peptide epitopes encoded in the minigene or the polyepitopic peptide), then assayed for peptide-specific cytotoxic activity in a 5lCr release assay. The results indicate the magnitude of the CTL response directed against the A2-restricted epitope, thus indicating the in vivo immunogenicity of the minigene vaccine and polyepitopic vaccine.

It is, therefore, found that the minigene elicits immune responses directed toward the HLA-A2 supermotif peptide epitopes as does the polyepitopic peptide vaccine. A similar analysis is also performed using other HLA-A3 and HLA-B7 transgenic mouse models to assess CTL induction by HLA-A3 and HLA-B7 motif or supermotif epitopes, whereby it is also found that the minigene elicits appropriate immune responses directed toward the provided epitopes.

To confirm the capacity of a class 11 epitope-encoding minigene to induce HTLs in vivo, DR transgenic mice, or for those epitopes that cross react with the appropriate mouse MHC molecule, l-Ab-restricted mice, for example, are immunized intramuscularly with 100 lig of plasmid DNA. As a means of comparing the level of HTLs induced by DNA immunization, a group of control animals is also immunized with an actual peptide composition emulsified in complete Freund's adjuvant.

CD4+ T cells, i. e. HTLs, are purified from splenocytes of immunized animals and stimulated with each of the respective compositions (peptides encoded in the minigene). The HTL response is measured using a 3H-thymidine incorporation proliferation assay, (see, e. g., Alexander ef al. Immunity 1 : 751-761, 1994). The results indicate the magnitude of the HTL response, thus demonstrating the in vivo immunogenicity of the minigene.

DNA minigenes, constructed as described in the previous Example, can also be confirmed as a vaccine in combination with a boosting agent using a prime boost protocol. The boosting agent can consist of recombinant protein (e. g., Barnett et aL, Aids Res. and Human Retroviruses 14, Supplement 3 : S299-S309, 1998) or recombinant vaccinia, for example, expressing a minigene or DNA encoding the complete protein of interest (see, e. g., Hanke et al., Vaccine 16 : 439- 445, 1998 ; Sedegah et al., Proc. Natl. Acad. Sci USA 95 : 7648-53, 1998 ; Hanke and McMichael, Immunol Letters 66 : 177- 181, 1999 ; and Robinson et al., Nature Med. 5 : 526-34, 1999).

For example, the efficacy of the DNA minigene used in a prime boost protocol is initially evaluated in transgenic mice. In this example, A2. 1/K'' transgenic mice are immunized IM with 100 ig of a DNA minigene encoding the immunogenic peptides including at least one HLA-A2 supermotif-bearing peptide. After an incubation period (ranging from 3- 9 weeks), the mice are boosted IP with 107 pfu/mouse of a recombinant vaccinia virus expressing the same sequence encoded by the DNA minigene. Control mice are immunized with 100 j. g of DNA or recombinant vaccinia without the minigene sequence, or with DNA encoding the minigene, but without the vaccinia boost. After an additional incubation period of two weeks, splenocytes from the mice are immediately assayed for peptide-specific activity in an ELISPOT assay.

Additionally, splenocytes are stimulated in vitro with the A2-restricted peptide epitopes encoded in the minigene and recombinant vaccinia, then assayed for peptide-specific activity in an alpha, beta and/or gamma IFN ELISA.

It is found that the minigene utilized in a prime-boost protocol elicits greater immune responses toward the HLA-A2 supermotif peptides than with DNA alone. Such an analysis can also be performed using HLA-A11 or HLA-B7 transgenic mouse models to assess CTL induction by HLA-A3 or HLA-B7 motif or supermotif epitopes. The use of prime boost protocols in humans is described below in the Example entitled"Induction of CTL Responses Using a Prime Boost Protocol." Example 24 : Peptide Compositions for Prophylactic Uses Vaccine compositions of the present invention can be used to prevent 109P1D4 expression in persons who are at risk for tumors that bear this antigen. For example, a polyepitopic peptide epitope composition (or a nucleic acid comprising the same) containing multiple CTL and HTL epitopes such as those selected in the above Examples, which are also selected to target greater than 80% of the population, is administered to individuals at risk for a 109P1 D4-associated tumor.

For example, a peptide-based composition is provided as a single polypeptide that encompasses multiple epitopes. The vaccine is typically administered in a physiological solution that comprises an adjuvant, such as incomplete Freunds Adjuvant. The dose of peptide for the initial immunization is from about 1 to about 50, 000 lAg, generally 100-5, 000 lg, for a 70 kg patient. The initial administration of vaccine is followed by booster dosages at 4 weeks followed by evaluation of the magnitude of the immune response in the patient, by techniques that determine the presence of epitope- specific CTL populations in a PBMC sample. Additional booster doses are administered as required. The composition is found to be both safe and efficacious as a prophylaxis against 109P1D4-associated disease.

Alternatively, a composition typically comprising transfecting agents is used for the administration of a nucleic acid- based vaccine in accordance with methodologies known in the art and disclosed herein.

Example 25 : Polyepitopic Vaccine Compositions Derived from Native 109P1D4 Sequences A native 109P1 D4 polyprotein sequence is analyzed, preferably using computer algorithms defined for each class I and/or class 11 supermotif or motif, to identify"relatively short"regions of the polyprotein that comprise multiple epitopes. The "relatively short"regions are preferably less in length than an entire native antigen. This relatively short sequence that contains multiple distinct or overlapping,"nested"epitopes can be used to generate a minigene construct. The construct is engineered to express the peptide, which corresponds to the native protein sequence. The"relatively short"peptide is generally less than 250 amino acids in length, often less than 100 amino acids in length, preferably less than 75 amino acids in length, and more preferably less than 50 amino acids in length. The protein sequence of the vaccine composition is selected because it has maximal number of epitopes contained within the sequence, i. e., it has a high concentration of epitopes. As noted herein, epitope motifs may be nested or overlapping (i e., frame shifted relative to one another). For example, with overlapping epitopes, two 9-mer epitopes and one 10-mer epitope can be present in a 10 amino acid peptide.

Such a vaccine composition is administered for therapeutic or prophylactic purposes.

The vaccine composition will include, for example, multiple CTL epitopes from 109P1 D4 antigen and at least one HTL epitope. This polyepitopic native sequence is administered either as a peptide or as a nucleic acid sequence which encodes the peptide. Alternatively, an analog can be made of this native sequence, whereby one or more of the epitopes comprise substitutions that alter the cross-reactivity and/or binding affinity properties of the polyepitopic peptide.

The embodiment of this example provides for the possibility that an as yet undiscovered aspect of immune system processing will apply to the native nested sequence and thereby facilitate the production of therapeutic or prophylactic immune response-inducing vaccine compositions. Additionally, such an embodiment provides for the possibility of motif- bearing epitopes for an HLA makeup (s) that is presently unknown. Furthermore, this embodiment (excluding an analoge embodiment) directs the immune response to multiple peptide sequences that are actually present in native 109P1D4, thus avoiding the need to evaluate any junctional epitopes. Lastly, the embodiment provides an economy of scale when producing peptide or nucleic acid vaccine compositions.

Related to this embodiment, computer programs are available in the art which can be used to identify in a target sequence, the greatest number of epitopes per sequence length.

Example 26 : Polyepitopic Vaccine Compositions from Multiple Antigens The 109P1 D4 peptide epitopes of the present invention are used in conjunction with epitopes from other target tumor-associated antigens, to create a vaccine composition that is useful for the prevention or treatment of cancer that expresses 109P1D4 and such other antigens. For example, a vaccine composition can be provided as a single polypeptide that incorporates multiple epitopes from 109P1D4 as well as tumor-associated antigens that are often expressed with a target cancer associated with 109P1 D4 expression, or can be administered as a composition comprising a cocktail of one or more discrete epitopes. Alternatively, the vaccine can be administered as a minigene construct or as dendritic cells which have been loaded with the peptide epitopes in vitro.

Example 27 : Use of peptides to evaluate an immune response Peptides of the invention may be used to analyze an immune response for the presence of specific antibodies, CTL or HTL directed to 109P1 D4. Such an analysis can be performed in a manner described by Ogg et al., Science 279 : 2103-2106, 1998. In this Example, peptides in accordance with the invention are used as a reagent for diagnostic or prognostic purposes, not as an immunogen.

In this example highly sensitive human leukocyte antigen tetrameric complexes ("tetramers") are used for a cross- sectional analysis of, for example, 109P1 D4 HLA-A*0201-specific CTL frequencies from HLA A*0201-positive individuals at different stages of disease or following immunization comprising a 109P1 D4 peptide containing an A*0201 motif. Tetrameric complexes are synthesized as described (Musey et al., N. Engf, J. Med. 337 : 1267, 1997). Briefly, purified HLA heavy chain (Ai0201 in this example) and ß2-microglobulin are synthesized by means of a prokaryotic expression system. The heavy chain is modified by deletion of the transmembrane-cytosolic tail and COOH-terminal addition of a sequence containing a BirA enzymatic biotinylation site. The heavy chain, ß2-microglobulin, and peptide are refolded by dilution. The 45-kD refolded product is isolated by fast protein liquid chromatography and then biotinylated by BirA in the presence of biotin (Sigma, St. Louis, Missouri), adenosine 5'triphosphate and magnesium. Streptavidin-phycoerythrin conjugate is added in a 1 : 4 molar ratio, and the tetrameric product is concentrated to 1 mglml. The resulting product is referred to as tetramer- phycoerythrin.

For the analysis of patient blood samples, approximately one million PBMCs are centrifuged at 300g for 5 minutes and resuspended in 50 ul of cold phosphate-buffered saline. Tri-color analysis is performed with the tetramer-phycoerythrin, along with anti-CD8-Tricolor, and anti-CD38. The PBMCs are incubated with tetramer and antibodies on ice for 30 to 60 min and then washed twice before formaldehyde fixation. Gates are applied to contain >99. 98% of control samples. Controls for the tetramers include both A*0201-negative individuals and A*0201-positive non-diseased donors. The percentage of cells stained with the tetramer is then determined by flow cytometry. The results indicate the number of cells in the PBMC sample that contain epitope-restricted CTLs, thereby readily indicating the extent of immune response to the 109P1 D4 epitope, and thus the status of exposure to 109P1 D4, or exposure to a vaccine that elicits a protective or therapeutic response.

Example 28 : Use of Peptide Epitopes to Evaluate Recall Responses The peptide epitopes of the invention are used as reagents to evaluate T cell responses, such as acute or recall responses, in patients. Such an analysis may be performed on patients who have recovered from 109P1D4-associated disease or who have been vaccinated with a 109P1 D4 vaccine.

For example, the class I restricted CTL response of persons who have been vaccinated may be analyzed. The vaccine may be any 109P1 D4 vaccine. PBMC are collected from vaccinated individuals and HLA typed. Appropriate peptide epitopes of the invention that, optimally, bear supermotifs to provide cross-reactivity with multiple HLA supertype family members, are then used for analysis of samples derived from individuals who bear that HLA type.

PBMC from vaccinated individuals are separated on Ficoll-Histopaque density gradients (Sigma Chemical Co., St.

Louis, MO), washed three times in HBSS (GIBCO Laboratories), resuspended in RPMI-1640 (GIBCO Laboratories) supplemented with L-glutamine (2mM), penicillin (50U/ml), streptomycin (50 gg/ml), and Hepes (10mM) containing 10% heat-inactivated human AB serum (complete RPMI) and plated using microculture formats. A synthetic peptide comprising an epitope of the invention is added at 10 Ilg/ml to each well and HBV core 128-140 epitope is added at 1 lg/ml to each well as a source of T cell help during the first week of stimulation.

In the microculture format, 4 x 105 PBMC are stimulated with peptide in 8 replicate cultures in 96-well round bottom plate in 100 ul/well of complete RPMI. On days 3 and 10, 100 pi of complete RPMI and 20 U/ml final concentration of rlL-2 are added to each well. On day 7 the cultures are transferred into a 96-well flat-bottom plate and restimulated with peptide, rIL-2 and 105 irradiated (3, 000 rad) autologous feeder cells. The cultures are tested for cytotoxic activity on day 14. A positive CTL response requires two or more of the eight replicate cultures to display greater than 10% specific 5aCr release, based on comparison with non-diseased control subjects as previously described (Rehermann, et at, Nature Med.

2 : 1104, 1108, 1996 ; Rehermann etal., J. Clin. Invest. 97 : 1655-1665, 1996 ; and Rehermann et al. J. Clin. Invest. 98 : 1432- 1440, 1996).

Target cell lines are autologous and allogeneic EBV-transformed B-LCL that are either purchased from the American Society for Histocompatibility and Immunogenetics (ASHI, Boston, MA) or established from the pool of patients as described (Guilhot, eta/. ; 1. Virol. 66 : 2670-2678, 1992).

Cytotoxicity assays are performed in the following manner. Target cells consist of either allogeneic HLA-matched or autologous EBV-transformed B lymphoblastoid cell line that are incubated overnight with the synthetic peptide epitope of the invention at 10 FM, and labeled with 100 IlCi of 51Cr (Amersham Corp., Arlington Heights, IL) for 1 hour after which they are washed four times with HBSS.

Cytolytic activity is determined in a standard 4-h, split well 51Cr release assay using U-bottomed 96 well plates containing 3, 000 targets/well. Stimulated PBMC are tested at effector/target (E/T) ratios of 20-50 : 1 on day 14. Percent cytotoxicity is determined from the formula : 100 x [(experimental release-spontaneous release) lmaximum release- spontaneous release)]. Maximum release is determined by lysis of targets by detergent (2% Triton X-100 ; Sigma Chemical Co., St. Louis, MO). Spontaneous release is <25% of maximum release for all experiments.

The results of such an analysis indicate the extent to which HLA-restricted CTL populations have been stimulated by previous exposure to 109P1 D4 or a 109P1 D4 vaccine.

Similarly, Class II restricted HTL responses may also be analyzed. Purified PBMC are cultured in a 96-well flat bottom plate at a density of 1. 5x105 cells/well and are stimulated with 10 lig/ml synthetic peptide of the invention, whole 109P1 D4 antigen, or PHA. Cells are routinely plated in replicates of 4-6 wells for each condition. After seven days of culture, the medium is removed and replaced with fresh medium containing 10U/ml L-2. Two days later, 1 IlCi 3H-thymidine is added to each well and incubation is continued for an additional 18 hours. Cellular DNA is then harvested on glass fiber mats and analyzed for 3H-thymidine incorporation. Antigen-specific T cell proliferation is calculated as the ratio of 3H- thymidine incorporation in the presence of antigen divided by the 3H-thymidine incorporation in the absence of antigen.

Example 29 : Induction Of Specific CTL Response In Humans A human clinical trial for an immunogenic composition comprising CTL and HTL epitopes of the invention is set up as an IND Phase I, dose escalation study and carried out as a randomized, double-blind, placebo-controlled trial. Such a trial is designed, for example, as follows : A total of about 27 individuals are enrolled and divided into 3 groups : Group l : 3 subjects are injected with placebo and 6 subjects are injected with 5 lig of peptide composition ; Group ll : 3 subjects are injected with placebo and 6 subjects are injected with 50 lig peptide composition ; Group III : 3 subjects are injected with placebo and 6 subjects are injected with 500 g of peptide composition.

After 4 weeks following the first injection, all subjects receive a booster inoculation at the same dosage.

The endpoints measured in this study relate to the safety and tolerability of the peptide composition as well as its immunogenicity. Cellular immune responses to the peptide composition are an index of the intrinsic activity of this the peptide composition, and can therefore be viewed as a measure of biological efficacy. The following summarize the clinical and laboratory data that relate to safety and efficacy endpoints.

Safety : The incidence of adverse events is monitored in the placebo and drug treatment group and assessed in terms of degree and reversibility.

Evaluation of Vaccine Efficacy : For evaluation of vaccine efficacy, subjects are bled before and after injection.

Peripheral blood mononuclear cells are isolated from fresh heparinized blood by Ficoll-Hypaque density gradient centrifugation, aliquote in freezing media and stored frozen. Samples are assayed for CTL and HTL activity.

The vaccine is found to be both safe and efficacious.

Example 30 : Phase tl Trials In Patients Expressing 109P1D4 Phase II trials are performed to study the effect of administering the CTL-HTL peptide compositions to patients having cancer that expresses 109P1 D4. The main objectives of the trial are to determine an effective dose and regimen for inducing CTLs in cancer patients that express 109P1 D4, to establish the safety of inducing a CTL and HTL response in these patients, and to see to what extent activation of CTLs improves the clinical picture of these patients, as manifested, e. g., by the reduction and/or shrinking of lesions. Such a study is designed, for example, as follows : The studies are performed in multiple centers. The trial design is an open-label, uncontrolled, dose escalation protocol wherein the peptide composition is administered as a single dose followed six weeks later by a single booster shot of the same dose. The dosages are 50, 500 and 5, 000 micrograms per injection. Drug-associated adverse effects (severity and reversibility) are recorded.

There are three patient groupings. The first group is injected with 50 micrograms of the peptide composition and the second and third groups with 500 and 5, 000 micrograms of peptide composition, respectively. The patients within each group range in age from 21-65 and represent diverse ethnic backgrounds. All of them have a tumor that expresses 109P1D4.

Clinical manifestations or antigen-specific T-cell responses are monitored to assess the effects of administering the peptide compositions. The vaccine composition is found to be both safe and efficacious in the treatment of 109P1D4- associated disease.

Example 31 : Induction of CTL Responses Using a Prime Boost Protocol A prime boost protocol similar in its underlying principle to that used to confirm the efficacy of a DNA vaccine in transgenic mice, such as described above in the Example entitled"The Plasmid Construct and the Degree to Which It Induces Immunogenicity,"can also be used for the administration of the vaccine to humans. Such a vaccine regimen can include an initial administration of, for example, naked DNA followed by a boost using recombinant virus encoding the vaccine, or recombinant protein/polypeptide or a peptide mixture administered in an adjuvant.

For example, the initial immunization may be performed using an expression vector, such as that constructed in the Example entitled"Construction of"Minigene"Multi-Epitope DNA Plasmids"in the form of naked nucleic acid administered IM (or SC or ID) in the amounts of 0. 5-5 mg at multiple sites. The nucleic acid (0. 1 to 1000 g) can also be administered using a gene gun. Following an incubation period of 3-4 weeks, a booster dose is then administered. The booster can be recombinant fowlpox virus administered at a dose of 5-107 to 5x109 pfu. An alternative recombinant virus, such as an MVA, canarypox, adenovirus, or adeno-associated virus, can also be used for the booster, or the polyepitopic protein or a mixture of the peptides can be administered. For evaluation of vaccine efficacy, patient blood samples are obtained before immunization as well as at intervals following administration of the initial vaccine and booster doses of the vaccine.

Peripheral blood mononuclear cells are isolated from fresh heparinized blood by Ficoll-Hypaque density gradient centrifugation, aliquote in freezing media and stored frozen. Samples are assayed for CTL and HTL activity.

Analysis of the results indicates that a magnitude of response sufficient to achieve a therapeutic or protective immunity against 109P1 D4 is generated.

Example 32 : Administration of Vaccine Compositions Using Dendritic Cells (DC) Vaccines comprising peptide epitopes of the invention can be administered using APCs, or"professional"APCs such as DC. In this example, peptide-pulsed DC are administered to a patient to stimulate a CTL response in vivo. In this method, dendritic cells are isolated, expanded, and pulsed with a vaccine comprising peptide CTL and HTL epitopes of the invention. The dendritic cells are infused back into the patient to elicit CTL and HTL responses in vivo. The induced CTL and HTL then destroy or facilitate destruction, respectively, of the target cells that bear the 109P1D4 protein from which the epitopes in the vaccine are derived.

For example, a cocktail of epitope-comprising peptides is administered ex vivo to PBMC, or isolated DC therefrom.

A pharmaceutical to facilitate harvesting of DC can be used, such as ProgenipoietinTM (Monsanto, St. Louis, MO) or GM- CSF/IL-4. After pulsing the DC with peptides, and prior to reinfusion into patients, the DC are washed to remove unbound peptides.

As appreciated clinically, and readily determined by one of skill based on clinical outcomes, the number of DC reinfused into the patient can vary (see, e. g., Nature Med. 4 : 328, 1998 ; Nature Med. 2 : 52, 1996 and Prostate 32 : 272, 1997).

Although 2-50 x 106 DC per patient are typically administered, larger number of DC, such as 107 or 108 can also be provided.

Such cell populations typically contain between 50-90% DC.

In some embodiments, peptide-loaded PBMC are injected into patients without purification of the DC. For example, PBMC generated after treatment with an agent such as ProgenipoietinTM are injected into patients without purification of the DC. The total number of PBMC that are administered often ranges from 108 to 1010. Generally, the cell doses injected into patients is based on the percentage of DC in the blood of each patient, as determined, for example, by immunofluorescence analysis with specific anti-DC antibodies. Thus, for example, if ProgenipoietinTM mobilizes 2% DC in the peripheral blood of a given patient, and that patient is to receive 5 x 106 DC, then the patient will be injected with a total of 2. 5 x 108 peptide-loaded PBMC. The percent DC mobilized by an agent such as Progenipoietin is typically estimated to be between 2-10%, but can vary as appreciated by one of skill in the art.

Ex vivo activation of CTL/HTL responses Alternatively, ex vivo CTL or HTL responses to 109P1D4 antigens can be induced by incubating, in tissue culture, the patient's, or genetically compatible, CTL or HTL precursor cells together with a source of APC, such as DC, and immunogenic peptides. After an appropriate incubation time (typically about 7-28 days), in which the precursor cells are activated and expanded into effector cells, the cells are infused into the patient, where they will destroy (CTL) or facilitate destruction (HTL) of their specific target cells, i. e., tumor cells.

Example 33 : An Alternative Method of Identifying and Confirming Motif-Bearing Peptides Another method of identifying and confirming motif-bearing peptides is to elute them from cells bearing defined MHC molecules. For example, EBV transformed B cell lines used for tissue typing have been extensively characterized to determine which HLA molecules they express. In certain cases these cells express only a single type of HLA molecule.

These cells can be transfected with nucleic acids that express the antigen of interest, e. g. 109PI D4. Peptides produced by endogenous antigen processing of peptides produced as a result of transfection will then bind to HLA molecules within the cell and be transported and displayed on the cell's surface. Peptides are then eluted from the HLA molecules by exposure to mild acid conditions and their amino acid sequence determined, e. g., by mass spectral analysis (e. g., Kubo et al., J.

Immunol. 152 : 3913, 1994). Because the majority of peptides that bind a particular HLA molecule are motif-bearing, this is an alternative modality for obtaining the motif-bearing peptides correlated with the particular HLA molecule expressed on the cell.

Alternatively, cell lines that do not express endogenous HLA molecules can be transfected with an expression construct encoding a single HLA allele. These cells can then be used as described, i. e., they can then be transfected with nucleic acids that encode 109P1 D4 to isolate peptides corresponding to 109P1 D4 that have been presented on the cell surface. Peptides obtained from such an analysis will bear motif (s) that correspond to binding to the single HLA allele that is expressed in the cell.

As appreciated by one in the art, one can perform a similar analysis on a cell bearing more than one HLA allele and subsequently determine peptides specific for each HLA allele expressed. Moreover, one of skill would also recognize that means other than transfection, such as loading with a protein antigen, can be used to provide a source of antigen to the cell.

Example 34 : Complementary Polynucleotides Sequences complementary to the 109P1D4-encoding sequences, or any parts thereof, are used to detect, decrease, or inhibit expression of naturally occurring 109P1 D4. Although use of oligonucleotides comprising from about 15 to 30 base pairs is described, essentially the same procedure is used with smaller or with larger sequence fragments.

Appropriate oligonucleotides are designed using, e. g., OLIGO 4. 06 software (National Biosciences) and the coding sequence of 109P1 D4. To inhibit transcription, a complementary oligonucleotide is designed from the most unique 5'sequence and used to prevent promoter binding to the coding sequence. To inhibit translation, a complementary oligonucleotide is designed to prevent ribosomal binding to a 109P1 D4-encoding transcript.

Example 35 : Purification of Naturally-occurring or Recombinant 109P1D4 Using 109P1D4Specific Antibodies Naturally occurring or recombinant 109P1D4 is substantially purified by immunoaffinity chromatography using antibodies specific for 109P1 D4. An immunoaffinity column is constructed by covalently coupling anti-109P1 D4 antibody to an activated chromatographic resin, such as CNBr-activated SEPHAROSE (Amersham Pharmacia Biotech). After the coupling, the resin is blocked and washed according to the manufacturer's instructions.

Media containing 109P1 D4 are passed over the immunoaffinity column, and the column is washed under conditions that allow the preferential absorbance of 109P1 D4 (e. g., high ionic strength buffers in the presence of detergent).

The column is eluted under conditions that disrupt antibody/109P1D4 binding (e. g., a buffer of pH 2 to pH 3, or a high concentration of a chaotrope, such as urea or thiocyanate ion), and GCR. P is collected.

Example 36 : Identification of Molecules Which Interact with 109P1D4 109P1D4, or biologically active fragments thereof, are labeled with 121 1 Bolton-Hunter reagent. (See, e. g., Bolton et al. (1973) Biochem. J. 133 : 529.) Candidate molecules previously arrayed in the wells of a multi-well plate are incubated with the labeled 109P1 D4, washed, and any wells with labeled 109P1 D4 complex are assayed. Data obtained using different concentrations of 109P1D4 are used to calculate values for the number, affinity, and association of 109P1D4 with the candidate molecules.

Example 37 : In Vivo Assay for 109P1 D4 Tumor Growth Promotion The effect of a 109P1 D4 protein on tumor cell growth is evaluated in vivo by gene overexpression in tumor-bearing mice. For example, SCID mice are injected subcutaneously on each flank with 1 x 106 of either PC3, DU145 or 3T3 cells containing tkNeo empty vector or a nucleic acid sequence of the invention. At least two strategies can be used : (1) Constitutive expression under regulation of a promoter such as a constitutive promoter obtained from the genomes of viruses such as polyoma virus, fowlpox virus (UK 2, 211, 504 published 5 July 1989), adenovirus (such as Adenovirus 2), bovine papilloma virus, avian sarcoma virus, cytomegalovirus, a retrovirus, hepatitis-B virus and Simian Virus 40 (SV40), or from heterologous mammalian promoters, e. g., the actin promoter or an immunoglobulin promoter, provided such promoters are compatible with the host cell systems, and (2) Regulated expression under control of an inducible vector system, such as ecdysone, tet, etc., provided such promoters are compatible with the host cell systems. Tumor volume is then monitored at the appearance of palpable tumors and followed over time to determine if the cells expressing a gene of the invention grow at a faster rate and whether tumors of a 109P1 D4 protein-expressing cells demonstrate characteristics of altered aggressiveness (e. g. enhanced metastasis, vascularization, reduced responsiveness to chemotherapeutic drugs).

Additionally, mice can be implanted with 1 x 105 of the same cells orthotopically to determine if a protein of the invention has an effect on local growth in the prostate or on the ability of the cells to metastasize, specifically to lungs, lymph nodes, and bone marrow.

The assay is also useful to determine the inhibitory effect of candidate therapeutic compositions, such as for example, 109P1 D4 protein-related intrabodies, 109P1 D4 gene-related antisense molecules and ribozymes.

Example 38 : 109P1D4 Monoclonal Antibody-mediated Inhibition of Tumors In Vivo The significant expression of 109P1 D4 proteins in the cancer tissues of Table I and its restrictive expression in normal tissues, together with its expected cell surface expression, makes 109P1 D4 proteins excellent targets for antibody therapy. Similarly, 109P1 D4 proteins are a target for T cell-based immunotherapy. Thus, for 109P1 D4 genes expressed, e. g., in prostate cancer, the therapeutic efficacy of anti-109P1 D4 protein mAbs in human prostate cancer xenograft mouse models is evaluated by using androgen-independent LAPC-4 and LAPC-9 xenografts (Craft, N., et a/.,. Cancer Res, 1999.

59 (19) : p. 5030-6) and the androgen independent recombinant cell line PC3-of 109P1 D4 (see, e. g., Kaighn, M. E., et al., Invest Urol, 1979. 17 (1) : p. 16-23) ; analogous models are used for other cancers.

Antibody efficacy on tumor growth and metastasis formation is studied, e. g., in a mouse orthotopic prostate cancer xenograft models and mouse kidney xenograft models. The antibodies can be unconjugated, as discussed in this Example, or can be conjugated to a therapeutic modality, as appreciated in the art. Anti-109P1 D4 protein mAbs inhibit formation of both the androgen-dependent LAPC-9 and androgen-independent PC3-109P1 D4 protein tumor xenografts. Anti-109P1 D4 protein mAbs also retard the growth of established orthotopic tumors and prolonged survival of tumor-bearing mice. These results indicate the utility of anti-109P1 D4 protein mAbs in the treatment of local and advanced stages of prostate cancer.

(See, e. g., (Saffran, D., et al., PNAS 10 : 1073-1078 or World Wide Web URL ww. pnas. org/cgi/doi/10. 1073/pnas. 051624698).

Administration of the anti-109P1 D4 protein mAbs lead to retardation of established orthotopic tumor growth and inhibition of metastasis to distant sites, resulting in a significant prolongation in the survival of tumor-bearing mice. These studies indicate that proteins of the invention are attractive targets for immunotherapy and demonstrate the therapeutic potential of anti-109P1 D4 protein mAbs for the treatment of local and metastatic cancer. This example demonstrates that unconjugated 109P1 D4 protein-related monoclonal antibodies are effective to inhibit the growth of human prostate tumor xenografts and human kidney xenografts grown in SCID mice ; accordingly a combination of such efficacious monoclonal antibodies is also effective.

Tumor inhibition using multiple unconjugated mAbs Materials and Methods 109P1D4 Protein-related Monoclonal Antibodies : Monoclonal antibodies are raised against proteins of the invention as described in the Example entitled "Generation of 109P1D4 Monoclonal Antibodies". The antibodies are characterized by ELISA, Western blot, FACS, and immunoprecipitation for their capacity to bind to the respective protein of the invention. Epitope mapping data for, e. g., the anti-109P1D4 protein mAbs, as determined by ELISA and Western analysis, indicate that the antibodies recognize epitopes on the respective 109P1 D4 protein. Immunohistochemical analysis of prostate cancer tissues and cells with these antibodies is performed.

The monoclonal antibodies are purified from ascites or hybridoma tissue culture supernatants by Protein-G Sepharose chromatography, dialyzed against PBS, filter sterilized, and stored at-20°C. Protein determinations are performed by a Bradford assay (Bio-Rad, Hercules, CA). A therapeutic monoclonal antibody or a cocktail comprising a mixture of individual monoclonal antibodies is prepared and used for the treatment of mice receiving subcutaneous or orthotopic injections of LAPC-9 prostate tumor xenografts.

Cancer Xenografts and Cell Lines The LAPC-9 xenograft, which expresses a wild-type androgen receptor and produces prostate-specific antigen (PSA), is passaged in 6-to 8-week-old male ICR-severe combined immunodeficient (SCID) mice (Taconic Farms) by s. c. trocar implant (Craft, N., et al., supra). The prostate carcinoma cell line PC3 (American Type Culture Collection) is maintained in RPMI supplemented with L-glutamine and 10% FBS.

Recombinant PC3 and 3T3-cell populations expressing a protein of the invention are generated by retroviral gene transfer as described in Hubert, R. S., et al., STEAP : a prostate-specific cell-surface antigen highly expressed in human prostate tumors. Proc Natl Acad Sci U S A, 1999. 96 (25) : p. 14523-8. Anti-protein of the invention staining is detected by using an FITC-conjugated goat anti-mouse antibody (Southern Biotechnology Associates) followed by analysis on a Coulter Epics-XL flow cytometer.

Xenograft Mouse Models.

Subcutaneous (s. c.) tumors are generated by injection of 1 x 10 6 LAPC-9, PC3, recombinant PC3-protein of the invention, 3T3 or recombinant 3T3-protein of the invention cells mixed at a 1 : 1 dilution with Matrigel (Collaborative Research) in the right flank of male SCID mice. To test antibody efficacy on tumor formation, i. p. antibody injections are started on the same day as tumor-cell injections. As a control, mice are injected with either purified mouse IgG (ICN) or PBS ; or a purified monoclonal antibody that recognizes an irrelevant antigen not expressed in human cells. In preliminary studies, no difference is found between mouse IgG or PBS on tumor growth. Tumor sizes are determined by vernier caliper measurements, and the tumor volume is calculated as length x width x height. Mice with s. c. tumors greater than 1. 5 cm in diameter are sacrificed. PSA levels are determined by using a PSA ELISA kit (Anogen, Mississauga, Ontario). Circulating levels of, e. g., anti-109P1 D4 protein mAbs are determined by a capture ELISA kit (Bethyl Laboratories, Montgomery, TX).

(See, e. g., Saffran, D., et al., PNAS 10 : 1073-1078 or www. pnas. orglcgil doi/10. 1073/pnas. 051624698) Orthotopic injections are performed under anesthesia by using ketamine/xylazine. For prostate orthotopic studies, an incision is made through the abdominal muscles to expose the bladder and seminal vesicles, which then are delivered through the incision to expose the dorsal prostate. LAPC-9 or PC3 cells (5 x 105) mixed with Matrigel are injected into each dorsal lobe in a 10-pl volume. To monitor tumor growth, mice are bled on a weekly basis for determination of PSA levels.

The mice are segregated into groups for the appropriate treatments, with anti-protein of the invention or control mAbs being injected i. p.

Anti-109P1 D4 Protein mAbs inhibit Growth of Respective 109P1 D4 Protein-Expressing Xenograft-Cancer Tumors The effect of anti-109P1 D4 protein mAbs on tumor formation is tested by using LAPC-9 and recombinant PC3- protein of the invention orthotopic models. As compared with the s. c. tumor model, the orthotopic model, which requires injection of tumor cells directly in the mouse prostate or kidney, respectively, results in a local tumor growth, development of metastasis in distal sites, deterioration of mouse health, and subsequent death (Saffran, D., et al., PNAS supra ; Fu, X., et al., Int J Cancer, 1992. 52 (6) : p. 987-90 ; Kubota, T., J Cell Biochem, 1994. 56 (1) : p. 4-8). The features make the orthotopic model more representative of human disease progression and allowed us to follow the therapeutic effect of mAbs on clinically relevant end points.

Accordingly, tumor cells are injected into the mouse prostate or kidney, and 2 days later, the mice are segregated into two groups and treated with either : a) 200-500, of anti-109P1 D4 protein Ab, or b) PBS three times per week for two to five weeks.

A major advantage of the orthotopic prostate-cancer model is the ability to study the development of metastases.

Formation of metastasis in mice bearing established orthotopic tumors is studied by IHC analysis on lung sections using an antibody against a prostate-specific cell-surface protein STEAP expressed at high levels in LAPC-9 xenografts (Hubert, R. S., et al., Proc Natl Acad Sci USA, 1999. 96 (25) : p. 14523-8).

Mice bearing established orthotopic LAPC-9 or recombinant PC3-109P1 D4 protein tumors are administered I OOOpg injections of either anti-109P1 D4 protein mAbs or PBS over a 4-week period. Mice in both groups are allowed to establish a high tumor burden (PSA levels greater than 300 ng/ml for IAPC-9), to ensure a high frequency of metastasis formation in mouse lungs. Mice then are killed and their prostate and lungs are analyzed for the presence of tumor cells by IHC analysis.

These studies demonstrate a broad anti-tumor efficacy of anti-109P1 D4 protein antibodies on initiation and progression of prostate cancer in xenograft mouse models. Anti-109P1 D4 protein antibodies inhibit tumor formation of both androgen-dependent and androgen-independent tumors, retard the growth of already established tumors, and prolong the survival of treated mice. Moreover, anti-109P1 D4 protein mAbs demonstrate a dramatic inhibitory effect on the spread of local prostate tumor to distal sites, even in the presence of a large tumor burden. Thus, anti-109P1 D4 protein mAbs are efficacious on major clinically relevant end points (tumor growth), prolongation of survival, and health.

Example 39 : Therapeutic and Diagnostic use of Anti-109P1 D4 Antibodies in Humans.

Anti-109P1 D4 monoclonal antibodies are safely and effectively used for diagnostic, prophylactic, prognostic and/or therapeutic purposes in humans. Western blot and immunohistochemical analysis of cancer tissues and cancer xenografts with anti-109P1 D4 mAb show strong extensive staining in carcinoma but significantly lower or undetectable levels in normal tissues. Detection of 109P1 D4 in carcinoma and in metastatic disease demonstrates the usefulness of the mAb as a diagnostic and/or prognostic indicator. Anti-109P1 D4 antibodies are therefore used in diagnostic applications such as immunohistochemistry of kidney biopsy specimens to detect cancer from suspect patients.

As determined by flow cytometry, anti-109P1 D4 mAb specifically binds to carcinoma cells. Thus, anti-109P1 D4 antibodies are used in diagnostic whole body imaging applications, such as radioimmunoscintigraphy and radioimmunotherapy, (see, e. g., Potamianos S., et. al. Anticancer Res 20 (2A) : 925-948 (2000)) for the detection of localized and metastatic cancers that exhibit expression of 109P1 D4. Shedding or release of an extracellular domain of 109P1 D4 into the extracellular milieu, such as that seen for alkaline phosphodiesterase B10 (Meerson, N. R., Hepatology 27 : 563-568 (1998)), allows diagnostic detection of 109P1D4 by anti-109P1 D4 antibodies in serum and/or urine samples from suspect patients.

Anti-109P1 D4 antibodies that specifically bind 109P1 D4 are used in therapeutic applications for the treatment of cancers that express 109P1 D4. Anti-109P1 D4 antibodies are used as an unconjugated modality and as conjugated form in which the antibodies are attached to one of various therapeutic or imaging modalities well known in the art, such as a prodrugs, enzymes or radioisotopes. In preclinical studies, unconjugated and conjugated anti-109P1 D4 antibodies are tested for efficacy of tumor prevention and growth inhibition in the SCID mouse cancer xenograft models, e. g., kidney cancer models AGS-K3 and AGS-K6, (see, e. g., the Example entitled"109P1D4 Monodona) Antibody-mediated Inhibition of Bladder and Lung Tumors In Vivo"). Either conjugated and unconjugated anti-109P1 D4 antibodies are used as a therapeutic modality in human clinical trials either alone or in combination with other treatments as described in following Examples.

Example 40 : Human Clinical Trials for the Treatment and Diagnosis of Human Carcinomas through use of Human AntHOSPIM Antibodies two Antibodies are used in accordance with the present invention which recognize an epitope on 109P1D4, and are used in the treatment of certain tumors such as those listed in Table I. Based upon a number of factors, including 109P1D4 expression levels, tumors such as those listed in Table) are presently preferred indications. In connection with each of these indications, three clinical approaches are successfully pursued.

I.) Adjunctive therapy : In adjunctive therapy, patients are treated with anti-109P1D4 antibodies in combination with a chemotherapeutic or antineoplastic agent and/or radiation therapy. Primary cancer targets, such as those listed in Table I, are treated under standard protocols by the addition anti-109P1D4 antibodies to standard first and second line therapy. Protocol designs address effectiveness as assessed by reduction in tumor mass as well as the ability to reduce usual doses of standard chemotherapy. These dosage reductions allow additional and/or prolonged therapy by reducing dose-related toxicity of the chemotherapeutic agent. Anti-109P1D4 antibodies are utilized in several adjunctive clinical trials in combination with the chemotherapeutic or antineoplastic agents adriamycin (advanced prostrate carcinoma), cispiatin (advanced head and neck and lung carcinomas), taxol (breast cancer), and doxorubicin (preclinical).

II.) Monotherapy : In connection with the use of the anti-109P1D4 antibodies in monotherapy of tumors, the antibodies are administered to patients without a chemotherapeutic or antineoplastic agent. In one embodiment, monotherapy is conducted clinically in end stage cancer patients with extensive metastatic disease. Patients show some disease stabilization. Trials demonstrate an effect in refractory patients with cancerous tumors. iii.) Imaging Agent : Through binding a radionuclide (e. g., iodine or yttrium (1131, Y90) to anti-109P1 D4 antibodies, the radiolabeled antibodies are utilized as a diagnostic and/or imaging agent. In such a role, the labeled antibodies localize to both solid tumors, as well as, metastatic lesions of cells expressing 109P1D4. In connection with the use of the anti-109P1 D4 antibodies as imaging agents, the antibodies are used as an adjunct to surgical treatment of solid tumors, as both a pre-surgical screen as well as a post-operative follow-up to determine what tumor remains and/or returns.

In one embodiment, a (111 in)-109P1D4 antibody is used as an imaging agent in a Phase I human clinical trial in patients having a carcinoma that expresses 109P1D4 (by analogy see, e. g., Divgi et al. J. Natl. Cancer Inst. 83 : 97-104 (1991)).

Patients are followed with standard anterior and posterior gamma camera. The results indicate that primary lesions and metastatic lesions are identified.

Dose and Route of Administration As appreciated by those of ordinary skill in the art, dosing considerations can be determined through comparison with the analogous products that are in the clinic. Thus, anti-109P1D4 antibodies can be administered with doses in the range of 5 to 400 mg/m 2, with the lower doses used, e. g., in connection with safety studies. The affinity of anti-109P1 D4 antibodies relative to the affinity of a known antibody for its target is one parameter used by those of skill in the art for determining analogous dose regimens. Further, anti-109P1D4 antibodies that are fully human antibodies, as compared to the chimeric antibody, have slower clearance ; accordingly, dosing in patients with such fully human anti-109P1D4 antibodies can be lower, perhaps in the range of 50 to 300 mg/m2, and still remain efficacious. Dosing in mg/m2, as opposed to the conventional measurement of dose in mg/kg, is a measurement based on surface area and is a convenient dosing measurement that is designed to include patients of all sizes from infants to adults.

Three distinct delivery approaches are useful for delivery of anti-1 09P1 D4 antibodies. Conventional intravenous delivery is one standard delivery technique for many tumors. However, in connection with tumors in the peritoneal cavity, such as tumors of the ovaries, biliary duct, other ducts, and the like, intraperitoneal administration may prove favorable for obtaining high dose of antibody at the tumor and to also minimize antibody clearance. In a similar manner, certain solid tumors possess vasculature that is appropriate for regional perfusion. Regional perfusion allows for a high dose of antibody at the site of a tumor and minimizes short term clearance of the antibody.

Clinical Development Plan (CDP) Overview : The CDP follows and develops treatments of anti-109P1 D4 antibodies in connection with adjunctive therapy, monotherapy, and as an imaging agent. Trials initially demonstrate safety and thereafter confirm efficacy in repeat doses. Trails are open label comparing standard chemotherapy with standard therapy plus anti-109P1 D4 antibodies. As will be appreciated, one criteria that can be utilized in connection with enrolment of patients is 109P1 D4 expression levels in their tumors as determined by biopsy.

As with any protein or antibody infusion-based therapeutic, safety concerns are related primarily to (i) cytokine release syndrome, i. e., hypotension, fever, shaking, chills ; (ii) the development of an immunogenic response to the material (i. e., development of human antibodies by the patient to the antibody therapeutic, or HAHA response) ; and, (iii) toxicity to normal cells that express 109P1D4. Standard tests and follow-up are utilized to monitor each of these safety concerns.

Anti-109P1D4 antibodies are found to be safe upon human administration.

Example 41 : Human Clinical Trial Adjunctive Therapy with Human Anti-109P1 D4 Antibody and Chemotherapeutic Agent A phase I human clinical trial is initiated to assess the safety of six intravenous doses of a human anti-109P1 D4 antibody in connection with the treatment of a solid tumor, e. g., a cancer of a tissue listed in Table I. In the study, the safety of single doses of anti-109P1 D4 antibodies when utilized as an adjunctive therapy to an antineoplastic or chemotherapeutic agent as defined herein, such as, without limitation : cisplatin, topotecan, doxorubicin, adriamycin, taxol, or the like, is assessed. The trial design includes delivery of six single doses of an anti-109P1 D4 antibody with dosage of antibody escalating from approximately about 25 mg/m 2to about 275 mg/m 2over the course of the treatment in accordance with the following schedule : Day 0 Day 7 Day 14 Day 21 Day 28 Day 35 mAb Dose 25 75 125 175 225 275 mglm 2 mgim 2 mgim 2 mgim 2 mgim 2 mgim 2 Chemotherapy + + + + + + (standard dose) Patients are closely followed for one-week following each administration of antibody and chemotherapy. In particular, patients are assessed for the safety concerns mentioned above : (i) cytokine release syndrome, i. e., hypotension, fever, shaking, chills ; (ii) the development of an immunogenic response to the material (i. e., development of human antibodies by the patient to the human antibody therapeutic, or HAHA response) ; and, (iii) toxicity to normal cells that express 109P1D4. Standard tests and follow-up are utilized to monitor each of these safety concerns. Patients are also assessed for clinical outcome, and particularly reduction in tumor mass as evidenced by MRI or other imaging.

The anti-109P1D4 antibodies are demonstrated to be safe and efficacious, Phase II trials confirm the efficacy and refine optimum dosing.

Example 42 : Human Clinical Trial : Monotherapy with Human Anti"109P1D4 Antibody Anti-109P1D4 antibodies are safe in connection with the above-discussed adjunctive trial, a Phase II human clinical trial confirms the efficacy and optimum dosing for monotherapy. Such trial is accomplished, and entails the same safety and outcome analyses, to the above-described adjunctive trial with the exception being that patients do not receive chemotherapy concurrently with the receipt of doses of anti-109P1 D4 antibodies.

Example 43 : Human Clinical Trial : Diagnostic Imaging with Anti-109P1 D4 Antibody Once again, as the adjunctive therapy discussed above is safe within the safety criteria discussed above, a human clinical trial is conducted concerning the use of anti-109P1D4 antibodies as a diagnostic imaging agent. The protocol is designed in a substantially similar manner to those described in the art, such as in Divgi et aL J. MaN. Cancer M. 83 : 97-104 (1991). The antibodies are found to be both safe and efficacious when used as a diagnostic modality.

Example 44 : 109P1D4 Functional Assays I. Phosphorylation of 109P1D4 on tyrosine residues One hallmark of the cancer cell phenotype is the active signal transduction of surface bound receptor molecules, such as the EGF receptor, through tyrosine phosphorylation of their cytoplasmic domains and their subsequent interaction with cytosolic signaling molecules. To address the possibility that 109P1 D4 is phosphorylated on its cytoplamsic tyrosine residues, 293T cells were transfected with the 109P1 D4 gene in an expression plasmid such that the 109P1 D4 gene was fused with a Myc/His tag, and were then stimulated with pervanadate (a 1 : 1 mixture of Na3VO4 and H202). After solubilization of the cells in Triton X-100, the 109P1D4 protein was immunoprecipitated with anti-His polyclonal antibody (pAb), subjected to SDS-PAGE and Western blotted with anti-phosphotyrosine. Equivalent immunoprecipitates were Western blotted with anti-His antibody. In Figure 22, 109P1D4 exhibits tyrosine phosphorylation only upon cell treatment with pervanadate and not without treatment. This suggests that pervanadate, which inhibits intracellular protein tyrosine phosphatases (PTPs), allows the accumulation of phosphotyrosine (tyrosine kinase activity) on 109P1D4. Further, a large amount of the 109P1D4 protein is sequestered into the insoluble fraction upon pervanadate activation, suggesting its association with cytoskeletal components. Similar effects of partial insolubility in Triton X-100 have been observed for cadherins, proteins that are related to protocadherins based on homology of their extracellular domains. Cadherins are known to interact with cytoskeletal proteins including actin, which are not readily soluble in the detergent conditions used in this study. Together, these data indicate that 109P1 D4 is a surface receptor with the capacity to be phosphorylated on tyrosine and to bind to signaling molecules that possess SH2 or PTB binding domains, including but not limited to, phospholipase-Cy1, Grb2, Shc, Crk, PI-3-kinase p85 subunit, rasGAP, Src-family kinases and abl-family kinases. Such interactions are important for downstream signaling through 109P1D4, leading to changes in adhesion, proliferation, migration or elaboration of secreted factors. In addition, 109P1D4 protein interacts with cytoskeletal components such as actin that facilitates its cell adhesion functions. These phenotypes are enhanced in 109P1D4 expressing tumor cells and contribute to their increased capacity to metastasize and grow in vivo.

Thus, when 109P1 D4 plays a role in cell signaling and phosphorylation, it is used as a target for diagnostic, prognostic, preventative and/or therapeutic purposes.

Example 45 : 109P1D4 RNA Interference (RNAi) RNA interference (RNAi) technology is implemented to a variety of cell assays relevant to oncology. RNAi is a post-transcriptional gene silencing mechanism activated by double-stranded RNA (dsRNA). RNAi induces specific mRNA degradation leading to changes in protein expression and subsequently in gene function. In mammalian cells, these dsRNAs called short interfering RNA (siRNA) have the correct composition to activate the RNAi pathway targeting for degradation, specifically some mRNAs. See, Elbashir S. M., et. al., Duplexes of 21-nucleotide RNAs Mediate RNA interference in Cultured Mammalian Cells, Nature 411 (6836) : 494-8 (2001). Thus, RNAi technology is used successfully in mammalian cells to silence targeted genes.

Loss of cell proliferation control is a hallmark of cancerous cells ; thus, assessing the role of 109P1D4 in cell survival/proliferation assays is relevant. Accordingly, RNAi was used to investigate the function of the 109P1D4 antigen. To generate siRNA for 109P1 D4, algorithms were used that predict oligonucleotides that exhibit the critical molecular parameters (G : C content, melting temperature, etc.) and have the ability to significantly reduce the expression levels of the 109P1D4 protein when introduced into cells. Accordingly, three targeted sequences for the 109P1D4 siRNA are : 5' MGAGGATACTGGTGAGATCT 3' (SEQ ID NO : 57) (oligo 109P1D4. a), 5'AAGAGCAATGGTGCTGGTAAA 3' (SEQ ID NO : 58) (oligo 109P1 D4. c), and 5'AACACCAGAAGGAGACAAGAT3' (SEQ ID NO : 59) (oligo 1 09P1 D4. d). In accordance with this Example, 109P1 D4 siRNA compositions are used that comprise siRNA (double stranded, short interfering RNA) that correspond to the nucleic acid ORF sequence of the 109P1 D4 protein or subsequences thereof. Thus, siRNA subsequences are used in this manner are generally 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or more than 35 contiguous RNA nucleotides in length. These siRNA sequences are complementary and non-complementary to at least a portion of the mRNA coding sequence. In a preferred embodiment, the subsequences are 19-25 nucleotides in length, most preferably 21-23 nucleotides in length. In preferred embodiments, these siRNA achieve knockdown of 109P1D4 antigen in cells expressing the protein and have functional effects as described below.

The selected siRNAs (109P1 D4. a, 109P1 D4. c, 109P1 D4. d oligos) were tested in LNCaP cells in the 3H-thymidine incorporation assay (measures cellular proliferation). Moreover, the oligonucleotides achieved knockdown of 109P1D4 antigen in cells expressing the protein and had functional effects as described below using the following protocols.

Mammalian siRNA transfections : The day before siRNA transfection, the different cell lines were plated in media (RPMI 1640 with 10% FBS w/o antibiotics) at 2x103 cells/well in 80 p (96 well plate format) for the proliferation assay.

In parallel with the 109P1 D4 specific siRNA oligo, the following sequences were included in every experiment as controls : a) Mock transfected cells with Lipofectamine 2000 (Invitrogen, Carlsbad, CA) and annealing buffer (no siRNA) ; b) Luciferase-4 specific siRNA (targeted sequence : 5'-AAGGGACGAAGACGAACACUUCTT-3') (SEQ ID NO : 60) ; and, c) Eg5 specific siRNA (targeted sequence : 5'-AACTGAAGACCTGAAGACAATAA-3') (SEQ ID NO : 61). SiRNAs were used at 10nM and ug/ml Lipofectamine 2000 final concentration.

The procedure was as follows : The siRNAs were first diluted in OPTIMEM (serum-free transfection media, Invitrogen) at 0. 1 pM (10-fold concentrated) and incubated 5-10 min RT. Lipofectamine 2000 was diluted at 10 pg/ml (10- fold concentrated) for the total number transfections and incubated 5-10 minutes at room temperature (RT). Appropriate amounts of diluted 1 0-fold concentrated Lipofectamine 2000 were mixed 1 : 1 with diluted 1 0-fold concentrated siRNA and incubated at RT for 20-30" (5-fold concentrated transfection solution). 20 pis of the 5-fold concentrated transfection solutions were added to the respective samples and incubated at 37oC for 96 hours before analysis.

3H-Thymidine incorporation assay : The proliferation assay is a 3H-thymidine incorporation method for determining the proliferation of viable cells by uptake and incorporation of label into DNA.

The procedure was as follows : Cells growing in log phase are trypsinized, washed, counted and plated in 96-well plates at 1000-4000 cells/well in 10% FBS. After 4-8 hrs, the media is replaced. The cells are incubated for 24-72 hrs, pulsed with 3H-Thy at 1. 5 pCi/ml for 14 hrs, harvested onto a filtermat and counted in scintillation cocktail on a Microbeta trilux or other counter.

In order to address the function of 109P1 D4 in cells, 109PI D4 was silenced by transfecting the endogenously expressing 109P1D4 cell line (LNCaP) with the 109P1D4 specific siRNAs (109P1D4. a, 109P1D4. c, and 109P1D4. d) along with negative siRNA controls (Luc4, targeted sequence not represented in the human genome), a positive siRNA control (targeting Eg5) and no siRNA oligo (LF2K) (Figure 23). The results indicated that when these cells are treated with siRNA specifically targeting the 109P1 D4 mRNA, the resulting"1 09P1 D def cient cells"showed diminished cell proliferation as measured by this assay (e. g., see oligo 109P1D4. a treated cells).

These data indicate that 109P1 D4 plays an important role in the proliferation of cancer cells and that the lack of 109P1 D4 clearly decreases the survival potential of these cells. It is to be noted that 109P1 D4 is constitutively expressed in many tumor cell lines. 109P1 D4 serves a role in malignancy ; its expression is a primary indicator of disease, where such disease is often characterized by high rates of uncontrolled cell proliferation and diminished apoptosis. Correlating cellular phenotype with gene knockdown following RNAi treatments is important, and allows one to draw valid conclusions and rule out toxicity or other non-specific effects of these reagents. To this end, assays to measure the levels of expression of both protein and mRNA for the target after RNAi treatments are important, including Western blotting, FACS staining with antibody, immunoprecipitation, Northern blotting or RT-PCR (Taqman or standard methods). Any phenotypic effect of the siRNAs in these assays should be correlated with the protein and/or mRNA knockdown levels in the same cell lines.

109P1D4 protein is reduced after treatment with siRNA oligos described above (e. g., 109PI D4. a, etc.) A method to analyze 109P1 D4 related cell proliferation is the measurement of DNA synthesis as a marker for proliferation. Labeled DNA precursors (i. e. 3H-Thymidine) are used and their incorporation to DNA is quantified.

Incorporation of the labeled precursor into DNA is directly proportional to the amount of cell division occurring in the culture.

Another method used to measure cell proliferation is performing cionogenic assays. In these assays, a defined number of cells are plated onto the appropriate matrix and the number of colonies formed after a period of growth following siRNA treatment is counted.

In 109P1D4 cancer target validation, complementing the cell survival/proliferation analysis with apoptosis and cell cycle profiling studies are considered. The biochemical hallmark of the apoptotic process is genomic DNA fragmentation, an irreversible event that commits the cell to die. A method to observe fragmented DNA in cells is the immunological detection of histone-complexed DNA fragments by an immunoassay (i. e. cell death detection ELISA) which measures the enrichment of histone-complexed DNA fragments (mono-and oligo-nucleosomes) in the cytoplasm of apoptotic cells. This assay does not require pre-labeling of the cells and can detect DNA degradation in cells that do not proliferate in vitro (i. e. freshly isolated tumor cells).

The most important effector molecules for triggering apoptotic cell death are caspases. Caspases are proteases that when activated cleave numerous substrates at the carboxy-terminal site of an aspartate residue mediating very early stages of apoptosis upon activation. All caspases are synthesized as pro-enzymes and activation involves cleavage at aspartate residues. In particular, caspase 3 seems to play a central role in the initiation of cellular events of apoptosis.

Assays for determination of caspase 3 activation detect early events of apoptosis. Following RNAi treatments, Western blot detection of active caspase 3 presence or proteolytic cleavage of products (i. e. PARP) found in apoptotic cells further support an active induction of apoptosis. Because the cellular mechanisms that result in apoptosis are complex, each has its advantages and limitations. Consideration of other criteria/endpoints such as cellular morphology, chromatin condensation, membrane blebbing, apoptotic bodies help to further support cell death as apoptotic. Since not all the gene targets that regulate cell growth are anti-apoptotic, the DNA content of permeabilized cells is measured to obtain the profile of DNA content or cell cycle profile. Nuclei of apoptotic cells contain less DNA due to the leaking out to the cytoplasm (sub-G1 population). In addition, the use of DNA stains (i. e., propidium iodide) also differentiate between the different phases of the cell cycle in the cell population due to the presence of different quantities of DNA in GO/G1, S and G2/M. In these studies the subpopulations can be quantified.

For the 109P1 D4 gene, RNAi studies facilitate the understanding of the contribution of the gene product in cancer pathways. Such active RNAi molecules have use in identifying assays to screen for mAbs that are active anti-tumor therapeutics. Further, siRNA are administered as therapeutics to cancer patients for reducing the malignant growth of several cancer types, including those listed in Table I. When 109P1D4 plays a role in cell survival, cell proliferation, tumorigenesis, or apoptosis, it is used as a target for diagnostic, prognostic, preventative and/or therapeutic purposes.

Throughout this application, various website data content, publications, patent applications and patents are referenced. (Websites are referenced by their Uniform Resource Locator, or URL, addresses on the World Wide Web.) The present invention is not to be limited in scope by the embodiments disclosed herein, which are intended as single illustrations of individual aspects of the invention, and any that are functionally equivalent are within the scope of the invention. Various modifications to the models and methods of the invention, in addition to those described herein, will become apparent to those skilled in the art from the foregoing description and teachings, and are similarly intended to fall within the scope of the invention. Such modifications or other embodiments can be practiced without departing from the true scope and spirit of the invention.

TABLES : TABLE) : Tissues that Express 109P1 D4 when malignant : Prostate Bladder Kidney Colon Lymphoma Lung Pancreas Ovary Breast Uterus Stomach Rectum Cervix Lymph Node Bone TABLE li : Amino Acid Abbreviations SINGLE LETTER THREE LETTER FULL NAME F Phe phenylalanine L Leu leucine S Ser serine Y Tyr tyrosine C Cys cysteine W Trp tryptophan P Pro proline H His histidine Q Gln glutamin R Arg arginine I lie isoleucine M Met methionine T Thr threonine N Asn asparagine K Lys Iysine V Val valine A Ala alanine D Asp aspartic acid E Glu lutamic acid G Gly glycine TABLE III : Amino Acid Substitution Matrix Adapted from the GCG Software 9. 0 BLOSUM62 amino acid substitution matrix (block substitution matrix). The higher the value, the more likely a substitution is found in related, natural proteins. (See world wide web URL ikp. unibe. ch/manual/blosum62. html) A C D E F G H I K L M N P Q R S T V W Y. 4 0-2-1-2 0-2-1-1-1-1-2-1-1-1 1 0 0-3-2 A 9-3-4-2-3-3-1-3-1-1-3-3-3-3-1-1-1-2-2 C 6 2-3-1-1-3-1-4-3 1-1 0-2 0-1-3-4-3 D 5-3-2 0-3 1-3-2 0-1 2 0 0-1-2-3-2 E 6-3-1 0-3 0 0-3-4-3-3-2-2-1 1 3 F 6-2-4-2-4-3 0-2-2-2 0-2-3-2-3 G 8-3-1-3-2 1-2 0 0-1-2-3-2 2 H 4-3 2 1-3-3-3-3-2-1 3-3-1 1 5-2-1 0-1 1 2 0-1-2-3-2 K 4 2-3-3-2-2-2-1 1-2-1 L 5-2-2 0-1-1-1 1-1-1 M 6-2 0 0 1 0-3-4-2 N 7-1-2-1-1-2-4-3 P 5 1 0-1-2-2-1 Q 5-1-1-3-3-2 R 4 1-2-3-2 S 5 0-2-2 T 4-3-1 V 11 2 W 7 Y TABLE IV : HLA Class I/II Motifs/Supermotifs TABLE IV (A) : HLA Class I Supermotifs/Motifs SUPERMOTIF POSITION POSITION POSITION 2 (Primary Anchor) 3 (Primary Anchor) C Terminus (Primary Anchor) A1 TILVMS FWY A2 LIVMATQ IVMATL A3 VSMATL/RK A24 YFWIVLMT FIYWLM B7 P VILFMWYA B27 RHK FYLWMIVA B44 ED FWYLIMVA B58 ATS FWYLIVMA B62 QLIVMP FWYMIVLA MOTIFS A1 TSM Y A1 DEAS A2. 1 LMVQIAT VLIMAT A3 LMVISATFCGD KYRHFA AHVTMDSAGNCDFKRYH A24 YFWM FLIW A*3101 MVTALIS RK A*3301 MVALFIST RK A*6801 AVTMSLI RK B*0702 P LMFWYAIV B*3501 P LMFWYIVA B51 P LIVFWYAM B*5301 P IMFWYAL V B*5401PATtVLMFtY Bolded residues are preferred, italicized residues are less preferred : A peptide is considered motif-bearing if it has primary anchors at each primary anchor position for a motif or supermotif as specified in the above table.

TABLE IV (B) : HLA Class II Supermotif 1 6 9 W, F, Y, V,. I, L A, V, I, L, P, C, S, T A, V, I, L, C, S, T, M, Y TABLE IV (C) : HLA Class II Motifs MOTIFS 1° anchor 1 2 3 4 1anchor6 7 8 9 DR4 preferred FMYLIVW M T I VSTCPALIM MH MH deleterious W R WDE "DR1preferredMFL/ViWPAMQVMATSPL/C MAVM deleterious C CH FD CWD GDE D DR7 preferred MFLIVWY M W A IVMSACTPL M IV deleterious C G GRD N G DR3 MOT ! FS 1°anchor1 2 3 fanchor4 5 1°anchor6 Motif a preferred LIVMFY D Motif b preferred LIVMFAY DNQEST KRH DR Supermotif MFLIVWY VMSTACPLI Italicized residues indicate less preferred or"tolerated"residues TABLE IV (D) : HLA Class I Supermotifs POSITION : 1 2 3 4 5 6 7 8 C-terminus SUPER- MOTIFS A1 1° Anchor 1° Anchor TILVMS FWY A2 1° Anchor 1° Anchor LIVMATQ LIVMAT. A3 Preferred 1° Anchor YFW YFW YFW P 1° Anchor VSMATLI (415) (3/5) (4/5) (4/5) RK deleterious DE (3/5) ; DE P (515) (4/5) A24 1° Anchor 1° Anchor YFWIVLMT FIYWLM B7 Preferred FWY (5/5) 1° Anchor FWY FWY 1"Anchor LIVM (3/5) P (4/5) (3/5) VILFMWYA deleterious DE (3/5) ; DE G QN DE P (5/5) ; (3/5) (4/5) (4/5) (4/5) G (4/5) ; A (315) ; QN (3/5) B27 1° Anchor 1°Anchor RHK FYLWMIVA B44 1° Anchor 1° Anchor ED FWYLIMVA B58 1° Anchor 1° Anchor ATS FWYLIVMA B62 1° Anchor 1° Anchor QLIVMP FWYMIVLA Italicized residues indicate less preferred or"tolerated"residues TABLE IV (E) : HLA Class I Motifs POSITION 1 2 3 4 5 6 7 8 9 C- terminus or C-terminus A1 preferred GFYW 1°Anchor DEA YFW P DEQN YFW 1Anchor 9-mer STM Y deleterious DE RHKLIVMP A G A A1 preferred GRHK ASTCLIVM 1°Anchor GSTC ASTC LIVM DE 1"Anchor 9-mer DEAS Y deleterious A RHKDEPYFW DE PQN RHK PG GP A1 preferred YFW 1Anchor DEAQN A YFWQN PASTC GDE P 1''Anchor 10-STM Y mer deleterious GP RHKGLIVM DE RHK QNA RHKYFW RHK A A1 preferred YFW STCLIVM 1 Anchor A YFW PG G YFW 1"Anchor 10-DEAS Y mer deleterious RHK RHKDEPYFW P G PRHK QN A2. 1 preferred YFW 1"Anchor YFW STC YFW A P 1"Anchor 9-mer LMIVQAT VLIMAT deleterious DEP DERKH RKH DERKH POSITION : 1 2 3 4 5 6 7 8 9 C- Terminus A2. 1 preferred AYFW 1°Anchor LVIM G G FYWL 1"Anchor 10-LMIVQAT VIM VLIMAT mer deleterious DEP DE RKHA P RKH DERKHRKH A3 preferred RHK 1"Anchor YFW PRHKYF A YFW P 1"Anchor LMVISATFCGD W KYRHFA deleterious DEP DE AH preferred A 1"Anchor YFW YFW A YFW YFW P 1"Anchor VTLMISAGNCD KRYH F deleterious DEP A G A24 preferred YFWRHK 1"Anchor STC YFW YFW 1"Anchor 9-mer YFWM FLIW deleterious DEG DE G QNP DERHKG AQN A24 Preferred 1"Anchor P YFWP P 1"Anchor 10-YFWM FLIW mer Deleterious GDE QN RHK DE A QN DEA A3101 Preferred RHK 1"Anchor YFW P YFW YFW AP 1 Anchor MVTALIS RK Deleterious DEP DE ADE DE DE DE A3301 Preferred 1"Anchor YFW AYFW 1"Anchor MVALFIST RK Deleterious GP DE A6801 Preferred YFWSTC 1°Anchor YFWLIV YFW P 1"Anchor AVTMSLI M RK deleterious GP DEG RHK A B0702Preferred RHKFWY 1°Anchor RHK RHK RHK RHK PA 1°Anchor P LMFi/l'YAI V deleterious DEQNP DEP DE DE GDE QN DE POSITION 1 2 3 4 5 6 7 8 9 C- terminus or C-terminus A1 preferred GFYW 1°Anchor DEA YFW P DEQN YFW 1°Anchor 9-mer STM Y deleteriousDE RHKLIVMP A G A A1 preferred GRHK ASTCLIVM 1°Anchor GSTC ASTC LIVM DE 1°Anchor 9-mer DEAS Y deleterious A RHKDEPYFW DE PQN RHK PG GP B3501Preferred FWYLIVM 1°Anchor FWY FWY 1°Anchor P LMFWY/V A deleterious AGP G G B51 Preferred LIVMFWY 1°Anchor FWY STC FWY G FWY 1°Anchor P LIVFWYA M deleterious AGPDER DE G DEQN GDE HKSTC B5301 preferred LIVMFWY 1°Anchor FWY STC FWY LIVMFWYFWY 1°Anchor P IMFWYAL V deleterious AGPQN G RHKQN DE B5401 preferred FWY 1°Anchor FWYLIVM LIVM ALIVM FWYA 1°Anchor P P ATIVLMF WY deleterious GPQNDE GDESTC RHKDE DE QNDGE DE TABLE IV (F) : Summary of HLA-supertypes Overall phenotypic frequencies of HLA-supertypes in different ethnic populations Specificity Phenotypic frequency SupertypePosition 2 C-TerminusCaucasianN. A. Black JapaneseChineseHispanic verage B7PAJLMVFWY43. 2 55. 157J43. 0 49. 3 i 9. 5 A3 AILMVST RK 37. 5 42. 1 45. 8 52. 7 43. 144. 2 A2 AILMVT AILMVT 45. 8 39. 0 42. 4 45. 9 43. 0 42. 2 A24 YF (WIVLMT) FL (YWLM) 23. 9 38. 9 58. 6 40. 1 38. 3 40. 0 B44 E (D) FWYLIMVA 43. 0 21. 2 42. 9 39. 1 39. 0 37. 0 1 I LVMS FWY 47. 1 16. 1 21. 8 14. 7 26. 3 25. 2 B27 RHK FYL (WMI) 28. 4 26. 1 13. 3 13. 9 35. 3 23. 4 B62 QL (IVMP) FWY MI 12. 6 4. 8 36. 5 25. 4 11. 1 18. 1 B58ATS FWY (L) V) 10. 0 5. 9 10. 3 TABLE IV (G) : lcalculated population coverage afforded by different HLA-supertype combinations HLA-supertypes Phenotypic frequency Caucasian N. A Blacks Japanese Chinese Hispanic Average 83. 0 86. 1 87. 5 88. 4 86. 3 86. 2 A2, A3 and B7 99.5 98.1 100.0 99. 5 99. 4 99. 3 A2, A3, B7, A24, B44 99. 9 99. 6 100. 0 99. 8 99. 9 99. 8 and A1 A2, A3, B7, A24, B44, A1, B27, B62, and B 58 Motifs indicate the residues defining supertype specificites. The motifs incorporate residues determined on the basis of published data to be recognized by multiple alleles within the supertype. Residues within brackets are additional residues also predicted to be tolerated by multiple alleles within the supertype.

Table V: Frequently Occurring Motifs Name avrg. % Description Potential Function identity Nucleic acid-binding protein functions as transcription factor, nuclear location zf-C2H2 34% Zinc finger, C2H2 type probable Cytochrome b (N- membrane bound oxidase, generate cytochrome b N 68% terminal)/b6/petB su eroxide domains are one hundred amino acids long and include a conserved lg 19% Immunoglobulin domain intradomain disulfide bond. tandem repeats of about 40 residues, each containing a Trp-Asp motif. Function in signal transduction and WD40 18% WD domain, G-beta repeat protein interaction may function in targeting signaling PDZ 23% PDZ domain molecules to sub-membranous sites LRR 28% Leucine Rich Repeat short sequence motifs involved in protein-protein interactions conserved catalytic core common to both serine/threonine and tyrosine protein kinases containing an ATP Pkinase 23% Protein kinase domain binding site and a catalytic site pleckstrin homology involved in intracellular signaling or as constituents PH 16% PH domain of the cytoskeleton 30-40 amino-acid long found in the extracellular domain of membrane- EGF 34% EGF-like domain bound proteins or in secreted proteins Reverse transcriptase RNA-dependent DNA Rvt 49% olymerase) Cytoplasmic protein, associates integral Ank 25% Ank repeat membrane proteins to the cytoskeleton NADH-membrane associated. Involved in Ubiquinone/plastoquinone proton translocation across the Oxidoredq132% complex)), various chains membrane calcium-binding domain, consists of a12 residue loop flanked on both sides by a Efhand 24% EF hand 12 residue alpha-helical domain Retroviral aspartyl Aspartyl or acid proteases, centered on Rvp 79% vrotease a catalytic aspartyl residue extracellular structural proteins involved in formation of connective tissue. The Collagen triple helix repeat sequence consists of the G-X-Y and the Collagen 62%'20 copies) polypeptide chains forms a triple helix. Located in the extracellular ligand- binding region of receptors and is about 200 amino acid residues long with two pairs of cysteines involved in disulfide Fn3 20% Fibronectin type III domain bonds seven hydrophobic transmembrane regions, with the N-terminus located 7 transmembrane receptor extracellularly while the C-terminus is 7tm_1 19% (rhodosin family) cytoplasmic. Signal through G proteins Table VI : Post-translational modifications of 109P1D4 O-glycosvlation sites 231 S 238 S 240 T 266 T 346 T 467 T 551 T 552 S 555 T 595 T 652 S 654 S 660 T 790 T 795 T 798 T 804 S 808 S 923 T 927 T 954 T 979 S 982 S 983 S 985 S 986 S 990 S 999 T 1000 T 1006 S 1017 S 1020 T Serine phosphorvlation sites 50 DLNLSLIPN (SEQ ID NO : 62) 147 VINISIPEN (SEQ ID NO : 63) 152 IPENSAINS (SEQ ID NO : 64) 238 ILQVSVTDT (SEQ ID NO : 65) 257 EIEVSIPEN (SEQ ID NO : 66) 428 LDYESTKEY (SEQ ID NO : 67) 480 PENNSPGIQ (SEQ ID NO : 68) 489 LTKVSAMDA (SEQ ID NO : 69) 495 MDADSGPNA (SEQ ID NO : 70) 559 TVFVSIIDQ (SEQ ID NO : 71) 567 QNDNSPVFT (SEQ ID NO : 72) 608 AVTLSILDE (SEQ ID NO : 73) 630 RPNISFDRE (SEQ ID NO : 74) 638 EKQESYTFY (SEQ ID NO : 75) 652 GGRVSRSSS (SEQ ID NO : 76) 654 RVSRSSSAK (SEQ ID NO : 77) 655 VSRSSSAKV (SEQ ID NO : 78) 656 SRSSSAKVT (SEQ ID NO : 79) 714 EVRYSIVGG (SEQ ID NO : 80) 789 LVRKSTEAP (SEQ ID NO : 81) 805 ADVSSPTSD (SEQ ID NO : 82) 808 SSPTSDYVK (SEQ ID NO : 83) 852 NKQNSEWAT (SEQ ID NO : 84) 877 KKKHSPKNL (SEQ ID NO : 85) 898 DDVDSDGNR (SEQ ID NO : 86) 932 FKPDSPDLA (SEQ ID NO : 87) 941 RHYKSASPQ (SEQ ID NO : 88) 943 YKSASPQPA (SEQ ID NO : 89) 982 ISKCSSSSS (SEQ ID NO : 90) 983 SKCSSSSSD (SEQ ID NO : 91) 984 KCSSSSSDP (SEQ ID NO : 92) 985 CSSSSSDPY (SEQ ID NO : 93) 990 SDPYSVSDC (SEQ ID NO : 94) 1006 EVPVSVHTR (SEQ ID NO : 95) Threonine phosphorylation sites 29 EKNYTIREE (SEQ ID NO : 96) 81 IEEDTGEIF (SEQ ID NO : 97) 192 DVIETPEGD (SEQ ID NO : 98) 252 VFKETEIEV (SEQ ID NO : 99) 310 TGLITIKEP (SEQ ID NO : 100) 320 DREETPNHK (SEQ ID NO : 101) 551 VPPLTSNVT (SEQ ID NO : 102) 790 VRKSTEAPV (SEQ ID NO : 103) 856 SEWATPNPE (SEQ ID NO : 104) 924 NWVTTPTTF (SEQ ID NO : 105) 927 TTPTTFKPD (SEQ ID NO : 106) 999 GYPVTTFEV (SEQ ID NO : 107) 1000YPVTTFEVP (SEQ ID NO : 108) Tyrosine phosphorylation sites 67 FKLVYKTGD (SEQ ID NO : 109) 158 INSKYTLPA (SEQ ID NO : 110) 215 EKDTYVMKV (SEQ ID NO : 111) 359 IDIRYIVNP (SEQ ID NO : 112) 423 ETAAYLDYE (SEQ ID NO : 113) 426 AYLDYESTK (SEQ ID NO : 114) 432 STKEYAIKL (SEQ ID NO : 115) 536 KEDKYLFTI (SEQ ID NO : 116) 599 TDPDYGDNS (SEQ ID NO : 117) 642 SYTFYVKAE (SEQIDNO : 118) 682 SNCSYELVL (SEQ ID NO : 119) 713 AEVRYSIVG (SEQ ID NO : 120) 810 PTSDYVKIL (SEQ ID NO : 121) 919 TMGKYNWVT (SEQ ID NO : 122) 989 SSDPYSVSD (SEQ ID NO : 123) 996 SDCGYPVTT (SEQ ID NO : 124) Table VII : Search Peptides 109P1D4 v. 1-9-mers, 10-mers and 15-mers (SEQ ID NO : 125) MDLLSGTYIF AVLLACWFH SGAQEKNYTI REEMPENVLI GDLLKDLNLS LIPNKSLTTA 60 MQFKLVYKTG DVPLIRIEED TGEIFTTGAR IDREKLCAGI PRDEHCFYEV EVAILPDEIF 120 RLVKIRFLIE DINDNAPLFP ATVINISIPE NSAINSKYTL PAAVDPDVGI NGVQNYELIK 180 SQNIFGLDVI ETPEGDKMPQ LIVQKELDRE EKDTYVMKVK VEDGGFPQRS STAILQVSVT 240 DTNDNHPVFK ETEIEVSIPE NAPVGTSVTQ LHATDADIGE NAKIHFSFSN LVSNIARRLF 300 HLNATTGLIT IKEPLDREET PNHKLLVLAS DGGLMPARAM VLVNVTDVND NVPSIDIRYI 360 VNPVNDTWL SENIPLNTKI ALITVTDKDA DHNGRVTCFT DHEIPFRLRP VFSNQFLLET 420 AAYLDYESTK EYAIKLLAAD AGKPPLNQSA MLFIKVKDEN DNAPVFTQSF VTVSIPENNS 480 PGIQLTKVSA MDADSGPNAK INYLLGPDAP PEFSLDCRTG MLTWKKLDR EKEDKYLFTI 540 LAKDNGVPPL TSNVTVFVSI IDQNDNSPVF THNEYNFYVP ENLPRHGTVG LITVTDPDYG 600 DNSAVTLSIL DENDDFTIDS QTGVIRPNIS FDREKQESYT FYVKAEDGGR VSRSSSAKVT 660 INWDVNDNK PVFIVPPSNC SYELVLPSTN PGTWFQVIA VDNDTGMNAE VRYSIVGGNT 720 RDLFAIDQET GNITLMEKCD VTDLGLHRVL VKANDLGQPD SLFSVVIVNL FVNESVTNAT 780 LINELVRKST EAPVTPNTEI ADVSSPTSDY VKILVAAVAG TITWWIFI TAVVRCRQAP 840 HLKAAQKNKQ NSEWATPNPE NRQMIMMKKK KKKKKHSPKN LLLNFVTIEE TKADDVDSDG 900 NRVTLDLPID LEEQTMGKYN WVTTPTTFKP DSPDLARHYK SASPQPAFQI QPETPLNSKH 960 HIIQELPLDN TFVACDSISK CSSSSSDPYS VSDCGYPVTT FEVPVSVHTR PVGIQVSNTT 1020 F 1021 109P1D4 v. 2 (both ends diff from v. 1) N'terminal 9-mers aa-30 to 8 MRTERQWVLIQIFQVLCGLIQQTVTSVPGMDLLSGTY (SEQ ID NO : 126) 1 0-mers aa-30 to 9 MRTERQWVLIQIFQVLCGLIQQTVTSVPGMDLLSGTYI (SEQ ID NO : 127) 15-mers aa-30 to 14 MRTERQWVLIQIFQVLCGLIQQTVTSVPGMDLLSGTYIFAVLL (SEQ ID NO : 128) 109P1D4 v. 2 C'Terminal 9 mers : aa 1004 to 1025 PVSVHTRPTDSRTSTIEICSEI (SEQ ID NO : 129) 10 mers : aa 1003 to 1025 VPVSVHTRPTDSRTSTIEICSEI (SEQ ID NO : 130) 15 mers : aa 997 to 1025 VTTFEVPVSVHTRPTDSRTSTIEICSEI (SEQ ID NO : 131) 109P1 D4 v. 3 9 mers : aa 1004 to 1347 (SEQ ID NO : 132) PVSVHTRPPMKEVVRSCTPMKESTTMEIWIHPQPQRKSEGKVAGKSQRRVTFHLPEGSQE SSSDG GLGDHDAGSLTSTSHGLPLGYPQEEYFDRATPSNRTEGDGNSDPESTFIPGLKKAAEITV QPTVE EASDNCTQECLIYGHSDACWMPASLDHSSSSQAQASALCHSPPLSQASTQHHSPRVTQTI ALCHS PPVTQTIALCHSPPPIQVSALHHSPPLVQATALHHSPPSAQASALCYSPPLAQAAAISHS SPLPQ VIALHRSQAQSSVSLQQGWVQGADGLCSVDQGVQGSATSQFYTMSERLHPSDD SIKVIPLTTFTP RQQARPSRGDSPMEEHPL 10 mers : aa 1003 to 1347 (SEQ ID NO : 133) VPVSVHTRPPMKEVVRSCTPMKESTTMEIWIHPQPQRKSEGKVAGKSQRRVTFHLPEGSQ ESSSD GGLGDHDAGSLTSTSHGLPLGYPQEEYFDRATPSNRTEGDGNSDPESTFIPGLKKAAEIT VQPTV EEASDNCTQECLIYGHSDACWMPASLDHSSSSQAQASALCHSPPLSQASTQHHSPRVTQT IALCH SPPVTQTIALCHSPPPIQVSALHHSPPLVQATALHHSPPSAQASALCYSPPLAQAAAISH SSPLP QVIALHRSQAQSSVSLQQGWVQGADGLCSVDQGVQGSATSQFYTMSERLHPSDDSIKVIP LTTFT PRQQARPSRGDSPMEEHPL 15 mers : aa 998 to 1347 (SEQ ID NO : 134) VTTFEVPVSV HTRPPMKEVV RSCTPMKEST TMEIWIHPQP QRKSEGKVAG KSQRRVTFHL PEGSQESSSD GGLGDHDAGS LTSTSHGLPL GYPQEEYFDR ATPSNRTEGD GNSDPESTFI PGLKKAAEIT VQPTVEEASD NCTQECLIYG HSDACWMPAS LDHSSSSQAQ ASALCHSPPL SQASTQHHSP RVTQTIALCH SPPVTQTIAL CHSPPPIQVS ALHHSPPLVQ ATALHHSPPS AQASALCYSP PLAQAAAISH SSPLPQVIAL HRSQAQSSVS LQQGWVQGAD GLCSVDQGVQ GSATSQFYTM SERLHPSDDS IKVIPLTTFT PRQQARPSRG DSPMEEHPL 109P1D4 v. 4 (deleting 10 aa, 1039-1048, from v. 1) 9-mers aa 1031-1056 (deleting 10 aa, 1039-1048, from v. 1) IWIHPQPQSQRRVTFH (SEQ ID NO : 135) 10-mers aa 1030-1057 (deleting 10 aa, 1039-1048, from v. 1) EIWIHPQPQSQRRVTFHL (SEQ ID NO : 136) 15-mers aa 1025-1062 (deleting 10 aa, 1039-1048, from v. 1) ESTTMEIWIHPQPQSQRRVTFHLPEGSQ (SEQ ID NO : 137) 109P1D4 v. 5 (deleting 37 aa, 1012-1048, from v. 1) 9-mers aa 1004-1056 (deleting 37 aa, 1012-1048, from v. 1) PVSVHTRPSQRRVTFH (SEQ ID NO : 138) 10-mers aa 1003-1057 (deleting 37 aa, 1012-1048, from v. 1) VPVSVHTRPSQRRVTFHL (SEQ ID NO : 139) 15-mers aa 998-1062 (deleting 37 aa, 1012-1048, from v. 1) VTTFEVPVSVHTRPSQRRVTFHLPEGSQ (SEQ ID NO : 140) 109P1D4 v. 6 (both ends difffrom v. 1) N'terminal 9-mers : aa-23 to 10 (excluding 1 and 2) MTVGFNSDISSWRVNTTNCHKCLLSGTYIF (SEQ ID NO : 141) 10-mers : aa-23 to 11 (excluding 1 and 2) MTVGFNSDISSVVRVNTTNCHKCLLSGTYIFA (SEQ ID NO : 142) 15-mers : aa-23 to 17 (excluding 1 and 2) MTVGFNSDISSVVRVNTTNCHKCLLSGTYIFAVLLVC (SEQ ID NO : 143) 109P1 D4 v. 6 C'terminal 9-mers : aa 1004-1016 PVSVHTRPTDSRT (SEQ ID NO : 144) 10-mers : aa 1003-1016 VPVSVHTRPTDSRT (SEQ ID NO : 145) 15-mers : aa 998-1016 VTTFEVPVSVHTRPTDSRT (SEQ ID NO : 146) 109P1 D4 v. 7 (N-terminal 21 aa difffrom those in v. 6) N'terminal 9-mers aa-21 to 10 (excluding 1 and 2) MFRVGFLIISSSSSLSPLLLVSWRVNTT (SEQ ID NO : 147) 10-mers aa-21 to 11 (excluding 1 and 2) MFRVGFLIISSSSSLSPLLLVSWRVNTTN (SEQ ID NO : 148) 15-mers aa-21 to 16 (excluding 1 and 2) MFRVGFLIISSSSSLSPLLLVSVVRVNTTNCHKCL (SEQ ID NO : 149) 109P1 D4 v. 8 9-mers aa 1099-1126 (excluding 1117 and 1118) TFIPGLKKEITVQPTV (SEQ ID NO : 150) 10-mers aa 1098-1127 (excluding 1117 and 1118) STFIPGLKKEITVQPTVE (SEQ ID NO : 151) 15-mers aa 1093-1131 (excluding 1117 and 1118) NSDPESTFIPGLKKEITVQPTVEEASDN (SEQ ID NO : 152) 109P1D4 v. 1, v. 2 and v. 3 SNP variants A15V 9-mers TYIFAVLLVCVVFHSGA (SEQ ID NO : 153) 10-mers GTYIFAVLLVCVVFHSGAQ (SEQ ID NO : 154) 15-mers MDLLSGTYIFAVLLVCVVFHSGAQEKNYT (SEQ ID NO : 155) 109P1D4 v. 1, v. 2 and v. 3 SNP variants M341 9-mers KNYTIREEIPENVLIGD (SEQ ID NO : 156) 10-mers EKNYTIREEIPENVLIGDL (SEQ ID NO : 157) 15-mers HSGAQEKNYTIREEIPENVLIGDLLKDLN (SEQ ID NO : 158) 109P1D4 v. 1, v. 2 and v. 3 SNP variants M341 and D42N 9-mers KNYTIREEIPENVLIGN (SEQ ID NO : 159) 10-mers EKNYTIREEIPENVLIGNL (SEQ ID NO : 160) 15-mers HSGAQEKNYTIREEIPENVLIGNLLKDLN (SEQ ID NO : 161) 109P1D4 v. 1, v. 2 and v. 3 SNP variants D42N 9-mers MPENVLIGNLLKDLNLS (SEQ ID NO : 162) 10-mers EMPENVLIGNLLKDLNLSL (SEQ ID NO : 163) 15-mers YTIREEMPENVLIGNLLKDLNLSLIPNKS (SEQ ID NO : 164) 109P1D4 v. 1, v. 2 and v. 3 SNP variants D42N and M341 9-mers IPENVLIGNLLKDLNLS (SEQ ID NO : 165) 10-mers EIPENVLIGNLLKDLNLSL (SEQ ID NO : 166) 15-mers YTIREEIPENVLIGNLLKDLNLSLIPNKS (SEQ ID NO : 167) 109P1D4 v. 1, v. 2 and v. 3 SNP variants A60T 9-mers IPNKSLTTTMQFKLVYK (SEQ ID NO : 168) 1 0-mers LIPNKSLTTTMQFKLVYKT (SEQ ID NO : 169) 1 5-mers DLNLSLIPNKSLTTTMQFKLVYKTGDVPLI (SEQ ID NO : 170) 109P1D4 v. 1, v. 2 and v. 3 SNP variants 1154V 9-mers ISIPENSAVNSKYTLPA (SEQ ID NO : 171) 10-mers NISIPENSAVNSKYTLPAA (SEQ ID NO : 172) 15-mers PATVINISIPENSAVNSKYTLPAAVDPDV (SEQ ID NO : 173) 109P1D4 v. 1, v. 2 and v. 3 SNP variants V2921 9-mers IHFSFSNLISNIARRLF (SEQ ID NO : 174) 10-mers KIHFSFSNLISNIARRLFH (SEQ ID NO : 175) 15-mers IGENAKIHFSFSNLISNIARRLFHLNATT (SEQ ID NO : 176) 109P1 D4 v. 1, v. 2 and v. 3 SNP variants T420N 9-mers FSNQFLLENAAYLDYES (SEQ ID NO : 177) 10-mers VFSNQFLLENAAYLDYEST (SEQ ID NO : 178) 15-mers FRLRPVFSNQFLLENAAYLDYESTKEYAI (SEQ ID NO : 179) 109P1D4 v. 1, v. 2 and v. 3 SNP variants T486M 9-mers NNSPGIQLMKVSAMDAD (SEQ ID NO : 180) 10-mers ENNSPGIQLMKVSAMDADS (SEQ ID NO : 181) 15-mers TVSIPENNSPGIQLMKVSAMDADSGPNAK (SEQ ID NO : 182) 109P1D4 v. 1, v. 2 and v. 3 SNP variants T486M and M491T 9-mers NNSPGIQLMKVSATDAD (SEQ ID NO : 183) 10-mers ENNSPGIQLMKVSATDADS (SEQ ID NO : 184) 15-mers TVSIPENNSPGIQLMKVSATDADSGPNAK (SEQ ID NO : 185) 109P1D4 v. 1, v. 2 and v. 3 SNP variants T486M and M491T and K500E 15-mers TVSIPENNSPGIQLMKVSATDADSGPNAE (SEQ ID NO : 186) 109P1D4 v. 1, v. 2 and v. 3 SNP variants T486M and K500E 15-mers TVSIPENNSPGIQLMKVSAMDADSGPNAE (SEQ ID NO : 187) 109P1D4 v. 1, v. 2 and v. 3 SNP variants M491T 9-mers IQLTKVSATDADSGPNA (SEQ ID NO : 188) 10-mers GIQLTKVSATDADSGPNAK (SEQ ID NO : 189) 15-mers ENNSPGIQLTKVSATDADSGPNAKINYLL (SEQ ID NO : 190) 109P1D4 v. 1, v. 2 and v. 3 SNP variants M491T and T486M 9-mers IQLNKVSATDADSGPNA (SEQ ID NO : 191) 10-mers GIQLNKVSATDADSGPNAK (SEQ ID NO : 192) 15-mers ENNSPGIQLNKVSATDADSGPNAKINYLL (SEQ ID NO : 193) 109P1D4 v. 1, v. 2 and v. 3 SNP variants M491T and T486M and K500E 10-mers GIQLNKVSATDADSGPNAE (SEQ ID NO : 194) 15-mers ENNSPGIQLNKVSATDADSGPNAEINYLL (SEQ ID NO : 195) 109P1 D4 v. 1, v. 2 and v. 3 SNP variants M491T and K500E 15-mers ENNSPGIQLTKVSATDADSGPNAEINYLL (SEQ ID NO : 196) 109P1D4 v. 1, v. 2 and v. 3 SNP variants K500E 9-mers DADSGPNAEINYLLGPD (SEQ ID NO : 197) 10-mers MDADSGPNAEINYLLGPDA (SEQ ID NO : 198) 15-mers TKVSAMDADSGPNAEINYLLGPDAPPEFS (SEQ ID NO : 199) 109P1D4 v. 1, v. 2 and v. 3 SNP variants K500E and M491T 10-mers TDADSGPNAEINYLLGPDA (SEQ ID NO : 200) 15-mers TKVSATDADSGPNAEINYLLGPDAPPEFS (SEQ ID NO : 201) 109P1D4 v. 1, v. 2 and v. 3 SNP variants K500E and M491T and T486M 15-mers MKVSATDADSGPNAEINYLLGPDAPPEFS (SEQ ID NO : 202) 109P1D4 v. 1, v. 2 and v. 3 SNP variants K500E and T486M 15-mers MKVSAMDADSGPNAEINYLLGPDAPPEFS (SEQ ID NO : 203) 109P1D4 v. 1, v. 2 and v. 3 SNP variants C517R 9-mers APPEFSLDRRTGMLTW (SEQ ID NO : 204) 10-mers DAPPEFSLDRRTGMLTVVK (SEQ ID NO : 205) 15-mers INYLLGPDAPPEFSLDRRTGMLTVVKKLDRE (SEQ ID NO : 206) 1ú9P1D v. 1, v. 2 and v. 3 SNP variants N576K 9-mers PVFTHNEYKFYVPENLP (SEQ ID NO : 207) 10-mers SPVFTHNEYKFYVPENLPR (SEQ ID NO : 208) 15-mers DQNDNSPVFTHNEYKFYVPENLPRHGTVG (SEQ ID NO : 209) 109P1D4 v. 1, v. 2 and v. 3 SNP variants S678Y 9-mers KPVFIVPPYNCSYELVLPS (SEQ ID NO : 210) 10-mers NKPVFIVPPYNCSYELVLPST (SEQ ID NO : 211) 15-mers VDVNDNKPVFIVPPYNCSYELVLPSTNPG (SEQ ID NO : 212) 109P1D4 v. 1, v. 2 and v. 3 SNP variants S678Y and C680Y 9-mers KPVFIVPPYNYSYELVLPS (SEQ ID NO : 213) 10-mers NKPVFIVPPYNYSYELVLPST (SEQ ID NO : 214) 15-mers VDVNDNKPVFIVPPYNYSYELVLPSTNPG (SEQ ID NO : 215) 109P1D4 v. 1, v. 2 and v. 3 SNP variants C680Y 9-mers VFIVPPSNYSYELVLPS (SEQ ID NO : 216) 10-mers PVFIVPPSNYSYELVLPST (SEQ ID NO : 217) 15-mers VNDNKPVFIVPPSNYSYELVLPSTNPGTV (SEQ ID NO : 218) 109P1D4 v. 1, v. 2 and v. 3 SNP variants C680Y and S678Y 9-mers VFIVPPYNYSYELVLPS (SEQ ID NO : 219) 10-mers PVFIVPPYNYSYELVLPST (SEQ ID NO : 220) 15-mers VNDNKPVFIVPPYNYSYELVLPSTNPGTV (SEQ ID NO : 221) 109P1D4 v. 1, v. 2 and v. 3 SNP variants T7901 9-mers INELVRKSIEAPVTPNT (SEQ ID NO : 222) 10-mers LINELVRKSIEAPVTPNTE (SEQ ID NO : 223) 15-mers VTNATLINELVRKSIEAPVTPNTEIADVS (SEQ ID NO : 224) 109P1D4 v. 1, v. 2 and v. 3 SNP variants K846M 9-mers HLKAAQKNMQNSEWATP (SEQ ID NO : 225) 10-mers PHLKAAQKNMQNSEWATPN (SEQ ID NO : 226) 15-mers RCRQAPHLKAAQKNMQNSEWATPNPENRQ (SEQ ID NO : 227) 109P1D4 v. 1, v. 2 and v. 3 SNP variants F855V 9-mers SPKNLLLNVVTIEETKA (SEQ ID NO : 228) 1 0-mers HSPKNLLLNVVTIEETKAD (SEQ ID NO : 229) 15-mers KKKKKHSPKNLLLNVVTIEETKADDVDSD (SEQ ID NO : 230) 109P1D4 v. 1, v. 2 and v. 3 SNP variants S958L 9-mers IQPETPLNLKHHIIQEL (SEQ ID NO : 231) 10-mers QIQPETPLNLKHHIIQELP (SEQ ID NO : 232) 15-mers PQPAFQIQPETPLNLKHHIIQELPLDNTF (SEQ ID NO : 233) 109P1D4 v. 1, v. 2 and v. 3 SNP variants K980N 9-mers FVACDSISNCSSSSSDP (SEQ ID NO : 234) 10-mers TFVACDSISNCSSSSSDPY (SEQ ID NO : 235) 15-mers LPLDNTFVACDSISNCSSSSSDPYSVSDC (SEQ ID NO : 236) Tables VIII-XXI : Table VIII-109P1D4v. 1-A1 Table VIII-109P1D4v. 1-A1- Table V ! ! I-109P1D4v. 1-A1- 9-mers. 9-mers 9-mers Each peptide is a portion of Each peptide is a portion of j Each peptide is a portion of SEQ iD NO : 3 ; each start SEQ ID NO : 3 ; each start SEQ ID NO : 3 ; each start position is specified, the position is specified, the s position is specified, the ') engthofpeptideis9amino j iengthofpeptideis9amino : iengthofpeptideis9amino j acids, and the end position for) acids, and the end position for) j acids, and the end position for) each peptide is the stars each peptide is the star each peptide is the start position plus eight position plus eighfi. y" position plus eight Start Subsequence ; Score StartSubsequence-Score ? Star ; y-Subsequence ; Sore MG_ 90. 000 399 1 FTDHEIPFR'25 000 ; ; 5 j FTTARID 1, 50- 700 AVDNDTGMN, ; 0. 500_, 189., VIETPEGDK ; 18. 000 779 ATLINELVR 1, 250 ; , 389 ;, DADHNGRVTj 0. 500, ; , [472-, ETIC7VHVFI, . 5. FOO 85-i7, Fv--T _PNR7 [. 0O. 4507 F ?-o f KVE D 9O Q7-27 60 475 278 IGENAKIHF ; 11. 250 j 858 jNPENRQMIM 1. 125, j 645 AEDGGRVSR 0. 500 : [9 FA : DGqLMfk- [ NA-VR-SIV, 0. 900 11 io, I-F FT7 492 DADSGPNAK 10 000 i ! 591 5--LITVTDPDY 1 000 : j 617 TIDSQTGVI 0. 500 2. 5 Di ECETPNHK, [-O999-1 78-0 INELV-R-. To- 370, LSENIPLNT v 6 750, _. j p 37 NVLIGDLLK_ m. 1 000 72 A (DQETGNI i 0 500 Fp LT,, KEqLmqK- iF T ? 5i DFT9EY F q o-7 :. . _........ .... .... _,. .......... I ........ _....... £ I. I.......... _. (. ,.......... : 1 [8C9, lTE 2. 250 [7FYEDKPV-l 0. 2 Qp- [ [SLDCrG 1. 800 (rLPDEFR5mf) nGMVUMo] 'BDEfFRLVK j 0] 'Fi EIEVSIPEN ! F727 QTG-NITL : 19. 675, fez 242 ; TNDNHPVFK : 00 854 WATPNPENR 1. 000. . 77 ; iEEDTGEIF.., 0. 450 "220iKVEDGGFPQ ; 4. 0 527, KLDREKEDK 1. 000 , 475 ; IPENNSPG 0. z "Y'rl ES"] E) PFRLR] [450j 951 ; QPETPLNSK : 4. 500 j 76 RIEEDTGEI 0. 900 109 EVEVAILPD 0. 450 807 TSDYVKILV : 3 750 ; 204 QKELDREK, 0900 ; 4014DHEIPFRLR 0. 450 '329 ASDGGLMPA ;. 3. 750 708 ; AEVRYSIV, 0. 900, ; 435 KLLAADAGK _, 0. 400, , b9 TAMQFKLVY ; 2. 500,' 316 ; DREETPNHK, 0900 f 780 ;, TLINELVRK = 0, 400 .. 738, KCDVTDLGL f 2 500 128 ; LIEDINDNA, 0., 900 , 256. VSIPENAPV 0, 300 354, SIDIRYIVN,,'2. 500 931 DSPDLARHY 0. 750 940 KSASPQPAF 0. 300 359,, VPSIDIRY ; 25J [. LTTAMQ) 0. 750" EI] 932 SPDLARHYK 2. 500, 981 CSSSSSDPY 0,. 750 744"LGLHRVLVK 0, 250, ; , 91, 1 ; LEEQTMGKY, j, 2"250, 55 ... KSLTTAMQF , 0 750'704 DTGMNAEVR ; 0. 250, 89 i MSTEAPVTP 2. 250, 635 KQESYTFYV e 0. 675 666, VNDNKPVFI ". 0. 2 253 ! EIEVSIPEN 1. 800 727 DQETGNITL ; 0. 675, 387 DKDADHNGR 0. 250 897 i DSDGNRVTL , 1. 500', 69 TGDVPLI I 0. 625 i 350, DNVPSfDIR [0.. 250, MDayVrol 804 SSPTSDYVK)"0. 600...,,. 'r68"n<TGD\/P f22l1 ! vEDGGFPQR ! ro. 500 TabieiX-109P1D4v. 1- DV7SDl 68 ; KTGDVPLIR'y1. 250, 221 r, VEDGGFPQR 0. 500 ! 'Tble IX-109P1D4v. 1- I 7-4-1- ! VTDLGLHRV ; 1. 250'201 j-LIVQKELDR r0. 500 _l_ _ .. A-10-mers j 273. ATDADIGEN ; 1, 250 609 ; ILDENDDFT, 0, 500 207 : 2lATDADI EN 60=9'F-L_ A792,, I, KADDVDSDG 1 I' O,. fc, Each peptide is a portion of) Table iX-109P1D4v. 1- Table iX-109P1D4V. 1- SEQ ID N0 : 3 ; each start < < ; 1 t 'position is specified, the"" position is specified, the Each peptideis a portion of achpeptideortionoT acids, and the end position for ! position is specified, the position is specified, the each peptide i the start I each peptide is the start position plus nine. 1 l acids, and ! he end position for ; acids, and the end poition fior each peptide 1, 9 the start each peptide is the start ; 989F LLETaAYLDY 225 000 j__Position plus nme. position plus nine. E 225. OOOE s i s Score 1X| RTGMITWKK | _1 000 ì t VNESvTNAyL i} 0. 450 j| iDHiif 2E00 4 ATLwR liim0 L J t ! ~. _ w ; iw 0 DTNDnHPVFKI i. ooo f tiFO0>K ; X00 t D 9 ß I. ! ~ _. =-, ~ =_ _ = _ __ e t => =_ =. =. . ~E ow>,,. w t 1 > e _ w1 * * _ S £ F 7 '366 VTDPdYGDNS'F 12 500 : . 659j TIEEtKADDV 0. 900 220 ; mQSAMIFIKVK 0. 300, ; F ff il q fl. f __ __, ~~ I tfl757$ii [ff0 ; 2wMLFIKI ; 0 . 000.......... !.... L-. ; IVTDPdYLD ! S, Fj Fi-- f+ tw [t [Ewl03 t S AS_t,. MW = _E., =, *e ! jf f f fff f 1 = lSll 1 [k. L25 $4071iYVKEf 5400 9 MmN-iw Fiv C0Wi . U. _^ Y _ 11 ». J If F =__ If ! EApPNfl1 ENDNaPVFTQaJ) Eo4SPRHY [2 f l i p f f. i f iu f f o.-J fF-~~S~ __ i _f f___f t____ ffg r f _ 1 8 LITIkEPLDR 0 500' 30 k, IPENaPVGTS 0. 225j HEWi fS f, _, _K, ___~_. _ ___ __ f r fif | uf i _. _ _... 2 AVDNdTGMNAi 2. 500 : j 1, 05 GLMPaRAMVL 0. 500'247 iPENnSPGIQ.. (0 225. jiR6iii 2. 500 g293t0MLTVvKKLDRflO5OO ti i303LEKE0) kYLFTI } 0. 225 ii g, JHN2ii 2. 500, i GLMPaRAMVLt 0. 500 « IgrlPENnspGlQ72 .-5oo-721 IqF ! gTPLNS 11 o. 600 i L\E ! PRHGTIE ? ? 5i 2 9 1, KLDReKEDKY F nii17fvTDvñDNVPSEt 2. 500 f [wtl i [ffi. J O} tNNSP IQLTK rOOn ! Siw ; w5OEg 1al IGENaK<01l 169 TCFTdHEIPF 0. 500 50 IGENaKIHFS 0, 225 I 1 _ _ 3 i_s _31 u J I i f r t f 2EO 1 : 1 GTITvVVYIF_j ET : K_ETaKLLAJ F-E22L7, |276flLLGPdãPPEF [2000 igrWDVnDNKPV {g 0500 i 0WIFiTAVVR Jl 0. 200 i| |IWT7 [ß00 7 i, 746tACDSiSKcss {, l 0 500 f i|3l LVLPsTNPGT | 0 200 i prDNTFlfTMO"6. DDYDSDGNMqq ======, , gYP T l500 735 -IQEL L NTF 1 350"I664 KAD.vDSDGN 0, 500 5-1-3-, V--TDLgLHRV ^ 1 250 i 396, VlRPnISFDR 0 500 j Table X-109P1 D4v. 1- wL7 fW <} WA D 45 ATDAdIGENA, 1 250 332 : IIDQnDNSPV 0 500 - r ---=------ Each peptide is a portio 0 a 11 VTDTnDNHPV, 1 250 ; 262AMDAdSGPNA ; Q 500 SEQ ID N0 : 3 ; each sfart 3 2. 75 0 g-I ' 'length of peptide is 9 amino' ; I il67 ! F length of peptide is 9 amino , 497 AID acids, and the end position for acids, and the end position forl < rwe 7 a R + 01 000 171q} SASPqPAFQI IL 0. 500 1 position plus eight t1 ' .... I . 9.. _ 5DLGLhRVLVKlToocr AI'ELVR] 500]) LFLLETAAYLj9 15--50. NATLiNELVR -0. 500'5 FLLETAAYL 8198.. 910 F-0. 500 7131 [§ : Sq position plus eight. LVF_Ed. 50 i7 FFLETA JE8198. L Table X-109P1 D4v 1 Table X-109P1 D4v. 1 Table X-109P1 D4v. 1- A0201-9-mers A0201-9-mers 1 1 A0201-9-mers _ _ _ ~ Each peptide is a portion of Each peptide is a portion of Each peptide is a portion of SEQ ID NO : 3 ; each start SEQ ID NO : 3 ; each start l {SEQ ID NO : 3 ; each start I position is specified, the {position is specified, the position is specified, the length of peptide is 9 amino t iength of peptide is 9 amino l} length of peptide is 9 amino acids, and the end position for ! acids, and the end position for, acids, and the end position for each peptide is the start. each peptide is the start each peptide is the start I position plus eight _ r position pius eight. ; i _ position plus eigt ! F (rF l. score fPo uece ) Score i..-,-0.. _............,.., I. GQPDSLFS I 6851 GLHRVLVKA} L 11. 426 825 FVTIEETKAI 2. 000 697 ! v Z 385. 691.... ».... GLMPARAM 691] F = a i =v =e ! = r _ = = .., , _. z". _. _.. ! .... # 354. QFLLETAAj 1. 864 "i 1 WLv"b_uA tk v. w-i Nurc W v 1 10. 931 FQ 86 765 [vW) Frrw] f423l --== 359 57 2, F4 !, FLMPARAMV T MVLVNVTD L- PARAMVLI, IL82û<TI ; < IRIQLHATDADI {S 10. 433 i GPNAKINYLUI 1764 w 7r ; ; v ; w w ß » =. M L° X vl\lrirL ou U 8 =QtQPETPL2Lg 903 l iEtLVLASDGGLt 12801 88. 043 : [275 1775 549 ;, ILDENDDFT, . 55 992 490 LTSNVTVFV 9 032 681'VTDLGLHRV 1. 511 W N, F V Ll i F- : 3 : 3 : 4 S ; KVINVVDV v Rgi ; jIQLTKw< Rjiai FLD E-1 [ : : 5 : : 9 : 971 1 F 8 vffp LGL-Rvi. ii 1 KvT-l F-8--Lg 42 (IQL K SAMIJ 7, ? 87 386'LNQSAMLFI 1. 465 g p ; GKY !'673 i mMEKCDV ; M76 J rf f. A mizif or oor. ff-= __ ff_, 6 _ 479 i TILAKDNGV 35 385 t'HEYNFY' 7--08 VNLFVNESV 1. 399 ; KEL 46 6. 086 r t-. ry N-y -N 4 iLvyKTGDvfff 31 ô4ô f 661 480 fffGVPPLTSNVf L 6. 086 i ì|515t fE 854 QTMGKYNW ; 29487 673 ITLMEKCDV,, 6076. ; 32-2 LITVTDKDA 1. 161" _I''. 076 'NPGTVVFQ°" fl ~. t = L_ _. I fl630il NPGTVVFQ Ii 6057 fl ffr | RQAPHLKAf| ... 67 f2L-VMVAGTff6 29. 137 f ll7573lfAVAGTITVVIL5. 739 224FjHiHr1 154 905 ; ELPLDNTFV28 690 ; 683 DLGLHRVLV5. 216. SLDCRTGM f ~ t 6 M I f l A g A) j f í 4 4 A, 4 IL23. w8J] iuirmf ff « l o0 ? fft6tfff L fif 930 SVSDV GYP 24. 952' 7, KEDKYL, F ! 3. 789, 267 v'GGL , 098 {ft {{SVSDCGYP Ig ft 11472llL<FEt 3. 789 I, [l fil VLASDGGL fl 1 jl.-.--Y i 75 NAPLFPATV'3. 671 831 [L ( ? LHRVLVIE. ? 16 L 4541 SffLDCLRTG7M -, ) HFSFSNn533l ' L 223 ; KIHFSFSNL ; 19. 533 1. 16 YELIKSQNI ; 3. 453 1...... 711 : FVNES A= 18. 856 ;, 493 NVTVFVSII 3. 271j 69 ; _SSTAILQVs 1. 044, T I _.... . 35 TPNTE (ADV 1044.. T i 1, 6. 5. 50'Fl 9-o FK-ETE (E-VSI F 7611YA-dTTv Hj T ; 16 1 6S ; ULSTRILQVSVJI 0. 966 ----ffi _ s $617w 1 lH6F MVAGH X6 _. f. _. TMGNW ) j) STAiL (WSVja966 9TTFEVFl4 : 654l [r, 756J. AAVAGT0 #5_J54 tG} KLLVLASDG | 0. 965 PSTNPGmfl M=Z I, M I, II 1366 (lY S , 366 YESTKEYAI 0. 933 625 ; PSTNPGT : ; .. 12 668 - FSLDCRTG 13. 997 4F5 2. 263 284 v 12. 226 743 ysSPTSDYy 2. 080j 658. GNTRDLFAi, 0 H< lW| DLFAIDQETJLE 1|3501lPVFSNQFLLII 0. 882 1 308,. wLSENIPL, 11 757, ; l _ ! .... 1 _ _ ; I_ I.. ___.- : . = l l TabieX-109P1D4v. 1- iATableXl-109P1D4v. 1-A02 1 : nTabl XI 1 P1 4 1 1 A0201-9-mers i. 10-mers i m A0201--En I 0-mers Each peptide is a portion of Each peptide is a portion of SEQ Each peptide is a portion of SEQ SEQ ID NO : 3 ; each start D NO : 3 ; each start position is ID NO : 3 ; each start position is position is specified, the specified, the length of peptide is j specified, the length of peptide is length of peptide is 9 amino 10 amino acids, and the end 10 amino acids, and the end acids, and the end position for position for each peptide is the position for each peptide is the } each peptide is the start start position plus nine.. start position plus nine. start position plus nine. start position plus nine. each pepfide is the start position plus eight. st Subsequence Score Subsequence 2arA IDI KlTItlAI 21 n Q77 ii... _ _... _, -_ [1x21=r, | IAL. 672 t NlTLmEKCDV. 9. 56. l454 12 SLDCrTGMLT t 2. 981 .......... W$TMGKyNWVTT.} 9. 149 | NlPLnTKIAL j 2. 937 12 10-mers LlIJLTDT, j) 8J20) jj09 j G'NGvQNYEL j) Z937 j 0-mers ; -mers, l. < =. =. ''"S'" ! rSnVf [757l"AVAGtiTV ,, V2. 2 \ 22 \ =2 C.....,... L. . . .. I pecified, the length of peptide is > - | 8 4< {g< [2 _9t 10 amino acids, and the end posibonforeachpeptideisthe | IIQEIPLDNT 12 8. 049 | i|37022| KEYAiKLLAA | 2. 488 j 1 0-mers startpositionplusnine. I il YPVTtFEVPV lw. l KINYILGPDA 21 2. 391 i l » IL.. 2, ~_. * = t_lt ~. _2 Each peptide is a portion of SEQ 22 274 jl LMPArAMVLV 21196. 4° ii21iiti i}} NVPSiDIRYI 29 54 | ILPDelFRLV jl184. 2152 S ; FR2 iw21 ILVAaVAGTI [2306 jl [ : 9O 2]-IIQEIPLDNT. 04l KEYAIKLLAA 2, 488 . < _.-2. =. ~. m = t 2 _ =. =.. _. | 701 SLFSvVIVNL 181. 794 500 IIDQnDNSPV. 6 503 I 632, GTVVfQVIAV : 2 222 ; .... . _.... position for each peptide is th 53 AILPdEIFRL ; 944. 9$1 , 629, TNPGtVVFQV 6. 057, 377 "LAADaGKPPL i 2. 068 start poi iloplu nine, 1R". °0zwl m9 <1 I323 t KlHFsFSNLV ll127. 193 1w<< w wEtv , 223 ; KINFsFSNLV wi 127. 1, 93., 414 =-S- (-PEn (SPGI'S. 881 647 ; MNAEvRYSiV : 1Y. 946 ; '279 AMVLv 115. 534 5T 7T I . L6 8 j 764. w M WVViFITAV 90. 423 ;,, 707 IVNLfVNESV 5. 069 307. , TVVLsENIPL ; 1 869, TH i0309 iL VLSEnlPLNT 1151. 940 [H151 t KTGDVPLIRI L SDGGL 4. 721 Ir n 2 A Ll-L D-e 1- 9 1-i I., 89 j 2] KILVAAVAGT-7] i. flILaKDNGV KNLLINFVTI VT I f .- m..... _ _... f W... y.. '. I . ...... .. ..., I.....-' 697 GQPDsLFSVV 22. 523, =680 DVTDlGl. HRV 4. 304,, 938. VTTFeVPVSV v 1m642, i l-.. W... w-al.. _.. ; I.. 4... e.... : .. _ :. ........ _. . : I V {t522 ASLPRhGTVGL 1121. 362 fi VVVlflTAW. j 4. 242 1 W LPLDnTFVAC. j 1589 | ; 522 ;, NLPRhGTVGL 21362 ; 1, 765T., VWIfITAW : 4. 242, ;, 906,, LPLDnTFVAC. 1., 589 1, TITVvVVIFI 18. 1A. 7". ; 300 ; IVNPvNDTVV 4. 242 422 GIQLtKVSAM 1. 571 ' I-å. ;. _ __ A 625 VLPStNPGTV ; 15 371 ; 197 I SIPEnAPVGT 4 201 ! ; 758 (VAGTiTWW 1. 549 1I Ir, ?, B1 _. o I j 711 j [7\/NEsVTNAT 1pZ298 (tf209prQLHaTDA1fY914" [620) CSYEiVLPSTreS I a. I ; i... 1.... ... __... f _.. 11......., . _ Rj} 711 il FVNEsVTNAT il 12 298 M L TQLHaTDADI 1F 11620 Rj CSYEIVLPST U 703 | FSWiVNLFV 11. 4871 ; 1 Wá LXCD TDL D : F IS-L 1435 11 , AX l OA = _, = MS _ S. _., l-. _ ! __ _ : l. . l _ _... _.. _. 696 LGQPdSLFSV 1, 0. 296 734.. VfPNtEIADV ; 3. 777 85,"NISIpENSAI'1435, I w o I l ~ A-L | 5 |I LVYKtGDVPL % l 10. 169 I} E} ãH1< T X, w Table XII-109P1 D4v. 1- MTable XII-109P1 D4v. 1- Table XII-109P1 D4v. 1= A3-9-mers L L 9-mers. z E] nU Ean 5En A Each peptide is a portion of SEQ Each peptide is a portion of SEQ Each peptide is a portion of SEQ ID NO : 3 ; each start position is i ID NO : 3 ; each start position is ; ID NO : 3 ; each start position is |specified, the length of peptide is 9 specified, the length of peptide is 91 specified, the length of peptide is 9* j amino acids, and the end position amino acids, and the end position amino acids, and the end position for each peptide is the start for each peptide is the start for each peptide is the start position plus eight. Q position plus eight. ! ! position plus eight. equ ___,- > < w [t rR A E __ CC. _. w. . . _ .... w_. _. C 13 KMPQLIVQI4'90 000 -76 TITV !// !/IF 0 900 ;."764 = ,/WIFITA j 0 270 ; F3-2-0---'i'IALITVTDK Fo-. 9-o 6"i, 234 NIARRLFHL 0. 270 467 KLDREKED 60. 000 117 ELIKSQNIF 0 900 : 475 KYLFTILAK 0. 270 ; [L5-j 37 j KLLMDAGK L90 000 320 l IALITVTDK å O. 900 i l. 234S NIARRLFHL j 0 ? 70 TLI ELVRK 145. 0 1-El _LKl__ ! Eo Lo-_KIRFLIEDI 0. 270 720 . TLINELVRK ; 45000 5., EIFRLVKIR 0 900 ; 64r., MKIRFLIEDI, 0. 270 ; I [XñFIHI <1 lffiooi A, jii 112 GVQNYELIK 36. 000 ; 701, SLFSVVIVN rv 7 0 900 ; 680 DVTDLGLHR 0 240 v dz __ .. lC 850 DLEEQTMGK 18. 000 389 SAMLFIKVK 0 675 ; i 476 : YLFTILAKD 0. 225 ; L YLFTILAKD 10. 2=2 5 t 805 ll IMMKKKKKK 125°°°l IL802 AL RQMIMMKKKjW 51 674 11 TLMEKCDVT 110. 225' .. ....... _.......... I......... t .. ... ... I L 803, .. QMIMMKKKK LKAAQK K. 000 ATLINELR-----1__72_1 [_ SPDLARHY-K IFP. ? 7 I.... MMKKKKKKK 110 0. 600 : 1'..... RCRQAPHLK 0. 200 t31 6 31 MMKKKKKKK 3wl 31 210 || QLHATDAD ! i || 775 | [RCROPHLK $ írb1 1r. åll wrj 7 460 GMLTVVKKL = 6. 075 489, PLTSNVTVF 0 600 464'VVKKLDREK 0 200 : 0 [-98-3 \i-TTF--0,-6 0-0 APHLKAAQK | 460 Ir GMLTVVKKL 3Re075 i| 489} | PLTSNVTVF 10600. 13 464 | VVKKLDREK li0W200. ...... S =.. = _= =.. =. 3 = ~ =. æ _. _ _ _. _ _ _ .. _. _. _ _.. ; _ 247 GLITIKEPL, 4. 050 462, LTVVKKLDR , 0 600 454, 3 T SLDCRTGML 0. 180 CDS SK lF470 C7 I FTTGARIDR ! Fo. 6ool 15-8 KVKVEDGGF 0. 1801 w=w AC1H3 A < [< C =We6Ej 31 [LGLHRVLVK X. 180 8=7 K [fOq-L FVNE'VT 241 ! F HLNATTGLI-0. 180'i L247 AL GLITIKEPL IL4. 0E IL. 4tl vl 0. 60t WL45w4-3LSLD RTGML ILO, 180 j 0 tA V'I 1 rV t. 3l 912 a} FVACDSISK 334. 000 X IL 25 11 FTTGARIDR 100. 600. IL 158 1 KVKVEDGGF 110. 180, wA V | 30 861 i31 WVTTPTTFK 1 A| m A| _rVVFQVA_ || 0. 180 j L<<3> lxr<w 3w3vH rX t 0E rP I ã 3 R C E | o-l 8 0 3 } rA V'rI t I rV E7 6-7] VIFI [ : : 5 : : 7 : jLQESTFV irglqi7, V A gA X __ _ _ _ _ = sA I V n X RVSRSSSAK 2. 60- ILVAAVA 1<1 ATTGLITIK 0 iXl RLFHLNATT 2 « li 1w31 VVLSENIPL iW 23XCEW3 3WCEH 1m+ [3 srosmre ìxr lIl ErP 31 590 31 RVSRSSSAK ll2. 0001 31 753 11 ILVMVAGT|t045 11 391 11 MLFIKVKDE 1911 F--T 7-1 L. Fj-Ll Em 0. 1=0,. tH1L KTGDVPLIR fil. 8001 33 891 f| QPETPLNSK ¢, Ot IL910'1 NTFVACDSI llO. 1501 , . 4 STNPGTWF ItlL AILPDEIFR llzii3 3XC iRiõil 3gXll STNPGTWF 1 804 IMMKKKKK j. 1. 500,, ! 531" LITVTDPDY 0. 400 523H3ES 3CE +H lf wff} ff f GLMPARAMV 1 1. 350 Table XI 11-109PI D4v. 1-A3- _..... _ __ _ Each peptide is a portion of SEQ 685 GLHRVLVKA 1. 350 , 942', EVPVSVHTR I 0 360 : Each peptide is a portion of SEQ _ _., I, ID N0 : 3 ; each start position is ! ! JiL ! Y9KELDRj [l] 2 LJ SSPTSDYVK JO. 300) specified, the length of peptide is i10 amino acids, and the end ......, _...,.. _ _ , 31",...-_ I f o rI position for each peptide is the if I p i [-1-2] l VIETPEGDK 0. 900 821 LLLNFVTIE 319 L 18. 000 431 458 riwiFrõU'31. 548 wirf. rh a lE5 3-0 GLITvTDPDY. , [ l. 00 IL129 11 VIETPEGDK fW3 it 821 3| LLLNi-VTIë XLO. 270 i li 319 iv, i 1800o il __ _ t. __ __ ___ f __ F _n ___ <, I t I I s i I WE < ii@riiEPoY ir31 Table XIII-109P1 D4v. 1 A3 Table Xiit-109P1 D4v. 1 A Table XIII-109P1 D4v. 1-A3- | 1 H. TM 10-mers 1 10-mers 1. 10-mers I 0-mers lo-m (10-mers Each peptide is a portion of SEQ !) Each peptide is a portion of SEQ ! Each peptide is a portion of SEQ ID NO : 3 ; each start position is) D NO : 3 ; each start position is specified, the length of peptide is specified, the length of peptide is specified, the length of peptide is 10 amino acids, and the end 10 amino acids, and the end 10 amino acids, and the end position for each peptide is the ! position for each peptide is the position for each peptide is the p _start position plus nine. start position plus nine. g Pos I Subsequence Score i Pos i Subsequence. Score í. Pos [Subsequence.'1 Score i , E|UKQESYTFYVK w Xt AlLPdEIFRL'w. 337 ; TCFTdHEIPF w C. _. v_. _ C _. X+E ES s__|_ ____ _s ~__ X z svse_Ne_ _, __ _1,. _ » X [wH S w 140 QLIVqKELDR', 12000 ; 522,. NLPRhGTVGL ;, m0. 600 , 454 SLDCrTGMLT : 0. 200 i score [K-7] eAE- D Ky 1---O NQFLIETAAY E3 QSAMLFIK 18 806 MMKKkKKKKK 10. 000. 761 TITVvWIFI 0. 540 418"NNSPgIQLTK v 4Y0. 180 | _,. x.. S _ __. J. W_ I j. __., _~_. _ _. «,. _-_ J. _ 1., t, r. ..., (......... : f......... tH. _273 (GLMPaRAMVL 8. 1. 00 : 123, ,,. N, IFGIDVIET : 0. 450, 217,., TTDIGEnAKIHF 0180_, lEl MLTVvKKLDR il 8. 000 i iXil VSSPtSDYVK ir0450 ! TWLsENIPL It 0. 1801i iX0L-L-ETaA-yLDy] iE9i. w i [0. 180_ MLTV, lv,, KK.. LD. R., I. i.... 8. 00, 0..... l......... .......... 1... _.. w.. .. r I.......... : I.... _........, . .......... _.,........ ... _...... : LILD nD 0-0-Nk gLiflK- F-o 9 o--. 11 ATLINELVRK 2. 250 823 LNFVTIEETK. 30 F33911_fTDHelPFRL-. 1 lEl HiCRõõl f DVGlnGVQNY il 0. 360. til il [<liw lil458Z< liUlwl ilwl =|8 °125°"1 } rl nr rlrrl rl r 564 VIRPnISFDR 2. 700 ; 655 IVGGnTRDLF ; T0. 300'321 £ ALITvTDKDA 0. 150 i u.... .... . .... ..... l_. , l. .. _. . ., L_... . _ m Il 77 Zl PLFPaTVINI kI 2. 700 Z il 243ZI NATTgLITIK Z| 0. 300 Zil iZI 26 IEL TTGArlDREK Z| 0. 150 Z Z0iZL VlRPnlSFDR ; Z ! 1 655 liZ IVGGnTRDLF ZZwZI ZlE. HõZZ 0. 150 i w | o3ooUl jZwZi} FTDHelpFRL i|013_ntZ 1X >R Z [<+ ijZI Z. °ZE res ro r mrol ltæ r 363 YLDYeSTKEY (2. 000" , 274 LMPArAMVLV ; 0. 300, 764 jWiFITAV ; 0. 135 wiEl YLDYeSTKEY 1w Z'274 iEi 0. 300 11 iZI 764 ZZEHii l 0. 135 Zi<X. iXl 0. 300 11 IZXlw3EX IEEZW TableXIV-109P1D4v. 1-Al101-lZ _YYVVIFITAV 0. 135 [7 : ] LMEKCDVTDL [i : 8-LO-1 F767] 1_"YlfltAyy C L , C809'L [ : ITI Table XIV-109PID4v. 1-Aiioi _-Ef E : SEQ ID NO : 3 ; each start E wiHN-i il positionisspecified, thelength ! S1 e w X õll ofpeptideis9aminoacids, and#, . | I 1 the end position for each, 1 !. ! _.. P ; , (., 'peptide is the start position plus ; peptide is the start position p 0. 270 ILL32, [ GTVVFQVIAV __eight. . '. I l. y' _. . .. ; .... 0 850, DLEEqTMGKY 0 810 ; 310 L-S-ENiPLNTK 0 225 i, 9 2 FVACDSISK y4. 000. F, iT, Fpp YkvNYIDV L2 NLLLNFVTIE _QNYIK 67 ! FLIEdINDNA 0 675 ; 241 HLNAtTGLIT v 0 200 ° 458 _ RTGMLTWK, 3 000. w .......... ..... ; I........ r........ .. .. . : Table X) V-109P1D4v. 1-A1101-) Table XiV-109P1D4v. 1-A1101- Table XtV-109P1D4v. 1-A1101- 9-mers 9-mers 9-mers Each peptide is a portion of) Each peptide is a portion of Each peptide is a portion of SEQ ID NO : 3 ; each start SEQ ID NO : 3 ; each start I SEQ ID NO. 3 ; each start position is specified, the length. position is specified, the length position is specified, the length of peptide is 9 amino acids, and of peptide is 9 amino acids, and of peptide is 9 amino acids, and the end position for each the end position for each the end position for each peptide is the start position ptus : {peptide is the start position pius ! peptide is the start position plus eight. eight, A H| Subsequence Xt Score. I rSubsequence ìl Score 11 l H| Subsequence i| Score I __ __ _"_ _w _ _ ..... _. ! t61''VVVTTPTTTK) 2. 000 t 563) [ GViRPNiSFj) 0. 180) 935 GYPyTTFEVJ 0. 036) j 861 WVTTPTTFK 2. 000' 563 ^GVIRPNISF j 0. 980, ! E [KDTY !) 0'J J]'D'} [T800']'IOESYTFYVK] roJ20 J)"843rF" [ 375 KLLAADAGK 1. 800 w ; . 56 QESYTFYVI. Oe10 !'43 , 1/TLDLP1DL. m0. 030, i ...... 11....... Score i Pos. FSubsey F----' -pos Subsequ. e. nc. e-. j. F9 £. 137 KMPQLIVQK t 1. 200 : 942 iEVPVSVHTR 0. 120, ; 280 , MVLVNVTDV, 0. 030# 3cx mr<w XEX 1. 800 M F F767 FITAYY Eto-i El2 IKDTYM 0. 030 t s w-E (KTGDVPLIR 1, T1200- 811, KKKKKHSPK 0. 060 762 ITVWVIFI 0. 030 ffi 1L137 XLKMPQLIVQK 11 1. 200. XI EVPVSVHTRt MVLVNVTDVi} } 0S3E XEFt iFESwE 1m [wE [<E11 vr i, f 1124411 ATTGLITIK t1 1. 000.} 68411 LGLHRVLVK 11 0. 060 11 1t7EVIFITAV il 0. 030 1 Mi bs SL46., 2 11 LTWKKLDR : l 311 t SENIPLNTK 10 0. 060 11 xS9t1 SNLVSNIARjS024 | 720 ; TLINELVRK I 0. 600 : ; 598 KVTINWDV k 0 060 ! 58 EIFRLVKIR'0. 024 1R1w133 fj fF61] FjVP- [ ...... 3N. : v.., w",.. _...,.,., 3. :."".. _".,. ,...,-,."", 7 ! [13- D : A : DqP- E8 : qT, 0. 400 1 Fl PKDDH _iE __AK [. 06L, 4 ! f'f'3'KVKDENDNA]'06'] [jL ! [ [EI E [T'J'LO" [liEOj 395 [ypND 803 [§M : l 757 IfYLGLI-Tyy E3 7j Fi _AL 0. 060 L , 320 IALITVTDK £ 0300 ; 158 KVKVEDGGF 0. 060, , 946 SVHTRPVGI, 0. 020 1 IwwawwJ _ w_ <t d E f s- Fi. Table XV-lO9PlD4v. 1- 1j7r= ?} V>> If Ms {QMIMMKKKK} 0300 11 308 11 VVLSENIPL 11 0. 0603 757 11 AVAGTITVV, LO. 020, i1 824 gI NFVTIEETK t1 0. 300. 11 61 11 RLVKIRFL1 11 0. 054 21 Iiml YVKILVMV'0. 020 53 1_5LPQLF.. Each peptide is a portion of SEQ ___w _=_ ____m_ww_l l_ww__ ~___www_ s k~~ t rww_wwz__wws wwvow __wwww_w1 IIKPDSPDLAR {l 0240 : ; KQESYTFYV} l 0054 01 li TableXV-109P1D4v. 1-t1 I---------^--|--X--t S i li A1101-10-mers 11 53 J) AiLPDEiFR 0. 240) 22 GEiFTTGAR) 0. 054J =-----=--- ;---- t""---.--.---------..-j----j Each peptide is a portion of SEQ I f. ; I.... ... _...... i ... __... i ID N0 : 3 ; each start position is iF-14TFI K 0. 240 632 specified, the length of peptide is h ww g 1 0 amino ac'ds, and the en | 10 amino acids, and the end rw__ t rW v V-? r-o -dWL VK 0. 200-- : 0. 040 start position plus nit ? '. iF| HLKMQKNK 11 0. 200. tW| SSPTSDYVK t| 0. 040 ! 1-*s-w _zv*~ = i v ol Jl MMKKKKKKK I 0. 200. IF NSPGIQLTK mI 0. 040 11 ìX|HõõCl ev r frov _l I-__ _, =, =_, _t, =_., < _ I : 1NR'i ifDK-I [T ? PO '891 ; QPETPLNSK 0. 200 ; 291 NVPSIDIRY 0 040I 719 i ATLInELVRK 1 500 [4 :] WEAFPN 3 7 LL, q Tt e. < T D% A1101-10-mers A1101-10-mers j A1101-10-mers Each peptide is a portion of SEQ Each peptide is a portion of SEQ Each pepfide is a portion of SEQ ID NO : 3 ; each start position is ID NO : 3 ; each start position is j) D NO : 3 ; each start position is specified, the length of peptide is specified, the length of peptide is, specified, the length of peptide is 10amino acids, and the end 10 amino acids, and the end 10 amino acids, and the end 'position for each peptide is the position for each peptide is the position for each peptide is the start position pius nine. start position plus nine. fl. start position pius nine. start position plus nine. rEEIIJ) fiD'TGViR] [''M'757]'GtiTyw] ['M20'] _ _ P = = A,'_ _ >= S =_ t Pos X Subsequencõ g l [H ; ; o I ; _s Subseguence ll Score j tiLA vwirv m v ms m fL9I DVIEtPEGDK L 0. 600 JH NGVQrfYEUK, OM [REeTPNHJK 020 = {M 5 = = = v | ; 766 WlFiTAWR ll 0. 600 N 823 | LNFVtlEETK I 0. 080 1 i 774 VRCRqAPHLKi 0. 020 ! * = -R a = « I u.... ..... . _. {3 _=_ ~ ~ _. _., _. _ _ _~ 0. _. _w __W _ wo 'EE93wj X ~ Li tE < E 804 MIMMkKKKKK 0 400 ; 601 INWdVNDNK 0. 060 ! 207 SVTQIHATDA 0. 020 ; aSs l ! ì } ? 8901 IQPEtPLNSK §1 0. 600 ß 31849 |pIDLEeQTMGK} 3 0. 060 3 31866 13TTFKpDSPDL|3 0. 020J start position plus nine. start position plus nine. r3l IMMKkKKKKK 10 0 ; 400 0 Iri30 KKKKkKHSPK lE 0. 060 1 3X1 TTFEvPVSVH 10 0. 020 3 fEt MYLdYESTK 1| 0. 400 ; {0YESTkEYAIK X| 0 060 X CRTGmLTVVK} | 0 020 LPDEiFRLVK 3X3 3Xw1-3> {0. 020 0 .. 3 r 3 Ir .. ^ _ ^. _ . _. _. _.. ___... __ _. _ (. _.. 181, DTNDnHPVFK 0 300 n 31 307 jF TWLsENIPL it 0. 060 1 ii 655 lt IVGGnTRDLF it 0. 020 I ^Y. e. ....... (.... ..... I T......... ; I. 1..... _.. tr80S<w} TWVvlFITA tt o. o60X1 1B3 1pVVRCrQAPHLlr O. 02 .. p _ . _ _ I. __. _.. _. _ , _, __. __ __ _. _.. : I . (.. ... . _ ßr=í 1t7 r m f<1rv F-AVqtl 'F-i7L F 0. 020 VEqqQRiF 1. 200 F757 140 QLfVqKELDR 0240 273 3GLMPaRAMVL 0. 048.. 530 GLITvTDPD 0. 018. _ | 652AlRYSIvGGNTRTl 0. 240 J 11 760 {TvVVVIF'iT 0. 045 I It, 446 {PDApPEFSLiT 0. 018 jlj . 24o F-O] l GL-lTvTqp ! K, _0. 018 T [Tw lW| 9 E ICWwF Tron rer Zor orv ZZZ VK, 0. 240 VD N-tT97MN : - ! 0. 018 (_M. _.... _. ri., W .. I 1..... .... _... l_ _, ...., I lr [ : 2 : 3 :] [ATTQLIT-IK 0. 1200 FTIDsQTGVi j--1 3 [ : SSPtSDYVK 0-IFL5-6j F 0 o-, 5 t w80 MMKKkKK K 0, 200'338"CFTDhEIPFR ; 0, 040 lTïi7 ZTHlliãAiROF Zl TableXVI-109PlD4v. 1-A24-Zl , _. .. _.. .. _.. _ _.. _. w.. _.. 1__. 030 Each peptide is a portion of T Zl 516 I2NFYVpENLPRT1 0. 160 Z 11 764 11 WWiFITAV'i 0. 030 1 11 r r r 11 w t S J s gI SEQ ID NO : 3 ; each start 11 __ : P P 9 TZ FõF 11°f peptide is 9 amino acids, andfl F7FLYqRG-L"j [-Q peptide is the start position plus 'F, F kv T- LPIQL. 1 2q7-HN) LNF-'EO3=0 eight. ) I s 1t ;. I_.. , 52. VAILpDEIFR : 0. 120 ; 765'VVVIfITAVV w.'0. 030,'Pos. Subsequencey T Score, - [200. 000 F26-, FT-TG F o-i o o--'FFogFGINGvQN-YEL 0024 26y . TTGArIDREK 0. 100. 109 GINGvQNYEL I 0. 024 6 Vl°KTGDVPLa 200. 000_ ; r r. u1 26, I TTGArlDREK 1| 0. 100. l fl 109 |IGiNGvQNYEL l 0. 024 I t1 6'|VYKTGDVPL'| 200. 000 |1 F8oo-JENRQmIMMKK'F o-. o24-, FKDSPDL LOCl F4 66 1 K-KLDREKEDK Fo ogo ! V7V 0. 090 858 IFON 21. 020 718 il NATLINELVR. 080_] 349 RPVFS=NQFL l-F43 : 1 :-] gDA=Dsq_YAK-0. E [ : i40=0 24 IFTTgARIDR 0 080 214 TDADiGENAK 0. 020, 688m. RVLVKANDL , 14. 400, ! E 1 v a- TabIeXVI-109P1D4v. 1-A24- TabIeXVI-109P1D4v. 1-A24 TabIeXVi-109P1D4v. 1-A24 9-mers 9-mers 9-mers Each peptide is a portion of : Each peptide is a portion of Each peptide is a portion of SEQ ID NO : 3 ; each start SEQ ID NO : 3 ; each start SEQ ID NO : 3 ; each start position is specified, the length position is specified, the length position is specified, the length of peptide is 9 amino acids, and of peptide is 9 amino acids, and of peptide is 9 amino acids, and) the end position for each the end position for each the end position for each i peptide is the start position plus | l peptide is the start position plus, peptide is the start position plus eight. I _ eight. . eight. i S [Fs--F- ) Pos) Subsequence) Score) i Pos j Subsequence) Score J j Posj Subsequence} Score J ; f _... .... I_........ _..... ....... I......... :. _.. 1.... : ! _.... _... _.. ... 1. _. . :... .. e i_ j 59 : IFRLVKIRF 14 000 :'368, STKEYAIKL 5. 2OT, 492_ . SNVTVFVSI _, ;. 2. 520_ ; 652 e RYSIVGGNT , 14 000 ; 703) FSWIVNLF 5040'i i 64,., KIRFLIEDI ^ 2. 400 ! 338.'CFTDHEIPF I 12. 000 l 371 mIKLLM 5. 000 j 344 IPF_PVF 2. 4 t F17 : 1 l i 621 riYELVLPST 0 500 ; ; 110T INGVQNYEL t 4. 400 # 817 SPKNLLLNF 2. 400, ; 749 : DYVKILVAA j 10 500 . 28 j GARIDREKL 4. 400 i 312 ENIPLNTKI ; 2. 376 i ! XE. w. wiEW t 2819L|iXi gi ! 3l2l i j w= » =_ XiXW iiW 'HW tEiviw [m liXiH3LV {iXERiwi I ít+ íiorol 3 ! GETYT-TF---K'F : . 25=0 4. 000 1 VNNYP§,, F El 7-y y -q pFA 9 _o-18 ? 7- [ : L : LLNYT, n l | < 2 ìr MLEY, y s-, FA-o2, 60 iXpw3iw, iHimæi C, Eiv3Wil Ir4 ~ S > ir R gri l i.. = A. _ ili r , __. . _, j... ., . ti} 935 |<l 8250 11 542, 2NSAVTLSILit 4. 000,'I 287 j<1 m1 102 ! AAVDPDVGI 1. 800' r 4<=r arraral YL i 7. 200 L 1 : P-,-F _O . T2 E qLL. 65-0--',, 1 678 KCOVTDLGL' 8 000 -158 K-VKVEDGGF 4 000 i i 820 ; NLLLNFVT j 1. 800 ; r. r Ir¢< e Ior. 1 'I 78. I LFPATVINI 1, 1 7. 500 I, L523 ; |LPRHGTVGLi, 4. 000,"'647 ItMNAEVRYSlt, 1. 680 n1 f 365 : DYESTKEYA3 7 500 16 ; RIEEDTGEI 3 960 186 ; HPVFKETEI 1. 650 , 6--tl EP q--S-- £ 436 ; GPNAKINYL j 7 200 : 445 I LGPDAPPEF ; 3. 960 ; 732,, RPVfPN'fEl 1. 650 54 : 1LPDEIFRL ; M7200, 502. DQNDNSPVF ! 3. 600 l 11, 1, y NGVQNYELI, 1. 500 s i ! 0X <w L > 7. 200''i''} 502JES3 s [BLEI Irivro r w r i r : [igET9 6. 000 Tabl f 717 TNATLINELw 6. 336 f ; I 117., ELIKSQNIF, ! 3. 600 (, | 1 § _ ____-_e _ ~ __M_ fW 402 A24-1 0-mers.......... 18 Each peptide is a portion of SEQ L : l. _.. ___. __.. _.. __.. i.. __ L _. _ l. _ Each peptide is a portion of SEQ 417, ENNSPGIQL 6., 000 181, DTNDNHPVF, 3 600",.. i.... j ID N0 : 3 ; each start position is ! specified, the length of peptide is LP NTKI 10 amino acids, and the end , . I. .- l-'.-. _..... _.. (- position for each peptide is the Lu 92,. ; SAINSKYTL ;.., 6 000 39 ; GIPRDEHCF 3 3. 000 !'P-os- ; S bsequence' : Score : -.-- ; I. _ ...... -'EY : NiylvEL, _l IFT -I F351 t| TPNHKLLVL IIt 6. 000 s GVIRPNISF, {3 000 t S st Hõ õoõTl Ifrv IXHi, jHiii, j so. oõo il f a If f tfwf.... _.. * ws } 227 I SFSNLVSNI f} 6. 00û''1 21811 IGENAKIHF Jl 3. 000 f iRA-ilfE. oõFl ! HõF i HH00 f <3H3'' f li 54i5iF_PENLlL5, 600 Ifmki. TITVVVVIF fll 2. 800g _ able XVII-109P1 D4v. 1- Tabe XVI-. T I I 109P1D4v1- TabIeXVII 109P1D4v1- A24-10-mers A24 10-mers 24, 10-mers Each peptide is a portion of SEQ Each peptide is a portion of SEQ Each peptide is a portion of SEQ ID NO : 3 ; each start position is ID NO : 3 ; each start position is ID NO : 3 ; each start position is specified, the length of peptide is specified, the length of peptide is specified, the length of peptide is 10 amino acids, and the end 10 amino acids, and the end 10 amino acids, and the end position for each peptide is the position for each peptide is the position for each peptide is the start position plus nine. start position plus nine. start position plus nine. HiH= kiEi2R E1 [j|iõF. l F-o--s ! F-ubsequnce Score F-g-s, IECO : r : (- __e k 239'LFHLnATTGL 20. 000' : 132 TPEGdKMPQLS V 6. 000'335 RVTCfiTDHEI' 2. 200 i4. 5 WLFTILAKD 2. 310 qKE l,, 4. 009 F5_,'IrTNhK 6. 000 F rwrto w H<R R<s EE3LA3 HE3LW [3wE [3 : : 35] v-LFl 16. 800 FT9 F : L : F L 858 'i EF : T : q : n-vL í Ww o R<r [H ï trs7 |X|KPPLnQSAML0 tml L D a G,. K. PpLl 4 800 | igj IVGGnTRDLF ij 2. 000 i 842 RVTLdLPIDL _ 9. 600 T 681 VTDLgLHRVL 4. 800 337, TCFTdHEIPF 2. 000. i.-,, 1... i,". t. t Pi 2. 000 9. 24r ! mmv iEwX L 1, | ESTKeYAIKL t ! 4400 1 t 1 2. 000 ! [- MPQLiVQKEL'9 240'367 ESTKeYAIKL 4. 400 ,, 859 YNWVtTPTTF ; 2 OOOj WL K l [XO-3rTITVWVIF tX00 1C < R (D7TF DSQTGVII 1. 800 i., 320, :, T-V : V- lF E246 TGLItIKEPL , 8. 400 773. VVRCrQAPHL 4000" ! 664^, ttFAIDqETGNI 1 800 IF 9. OOiF 701 F-T VN r-PUF 1. 800 . 40, 4. 000, [6 1. _FA [PgTGL 1. 800 1 ySnA5 8. 400 971 1 SAINSKYTL 1 4. 000 ;, x 731 ; EAPVtPNTEI , 1. 650 897, NSKHhIIQEL w 7, 392 ; 6931 ANDLgQPDSL'4. 000 T 744,,, SSPTsDYVKI 1. 650^j WH w l<< i ; f wr v . Hew IXEV3@v EE r< } EST rvw ï i, W, 1wW o r ; 1=_ I _ im o 53"AILPdEIFRL 7. 200 "541 DNSAvTLSIL, 4. 000 Table XVlll-109P1 D4v. 1-B7 m lFmv . waivrX H r l+ 1 0ReLE |WIwHõõõX |l,,."., _,.,,-rners ll Each peptide is a portion of 1r f. il SEQ ID NO : 3 ; each start position is specified, the iw_ {1 6151 VPPSnCSYEL ! 6. 600 816'JHSPKnLLLNFJ ! 3. 600 ngth of peptide is 9 amino 5I 1acids, and the end position for each peptide is the start 0 position pi 313 NIPLnTKIAL 6000, 343 EIPFrLRPVF 3. 600, position plus eight. ; i [EoIL ! seq ence F ; _ = _ _ _ w_ _ _ I ~ w _ _ _ _ í., t ISWãI H00H llWl lHlHõõC W1 523'I LPRHGTVGL J 1800. 000 Hi-oF 0 HXooF ; 1 28 I GARIDREKL 1180. 000 v s r w 265'LLVLaSDGGL, 6. 000 58, EIFRIVKIRF 2. 800 314 I. P, LNTKIAL,. 80 000 ;, |265i|LLVLaSDGGL | 6. 000 1 iFHõF'13141 IPLNTKIAL. 1 80. 000 1, l iF-F-6, 000 1 F-43-6, F- 1202 öõF 1452yWC285oo ll30211 NPVNDTVVL'<1 _. _... _ I _....... ... ! _.... 233 SNIArRLFHL_ 6. 0 217 DIGEnAKIHF, 2. 400 _j = 732 APVTPNTEI 36. 000,, w w3 ç . Table XVIII-109P1 D4v. 1 B7 Table XVIII-109P1 D4v. 1-B7 Table XVIII-109P1 D4v. 1-B7 9-mers S'fsrs 9-mers Each peptide is a portion of Each peptide is a portion of Each peptide is a portion of SEQ ID NO : 3 ; each start SEQ ID NO : 3 ; each start SEQ ID NO : 3 ; each start position is specified, the position is specified, the position is specified, the length of peptide is 9 amino length of peptide is 9 amino length of peptide is 9 amino acids, and the end position for acids, and the end position for acids, and the end position for each peptide is the start each peptide is the start each peptide is the start position plus eight. position plus eight position plus eight. J (Pos !) Subsequence j Score Posj) Subsequence ! Score fjppsjjSubsequencej) Score ...... iFL Yp -syT Fl. 200 [[ELIVGGNTRDLJL2O*OOOSI | VTLDLPIDL t| 4000 0 DQETGNTL tt 1. 200 655 ; IVGGNTRDL : 20. 000 843. VTLDLPIDL 4. 000 ; i 667 DQETGNITL 1. 200, 688j wNDL. 20. 00t 542 NSAVTLSIL X 4. 000 i. 454 SLDCRTGML. 1. 200 l 20. 00 7L4- LDCR-Tqy 1 1, 200 » E i isl 1. 200 1 E [Er3 H < : E iRE [X : K PQEIFRLV =v-w~ ==-w ; u = v 266. wH0-DoooT 515i YNFYVPENL 4. 000 1 2801 MVLVNVTDVj 1. 000 j L ar w = W<|E-ooM i 750 YVKILVMV li 1. 000 1 e =-w e- i gj H w S w H : F H rWiFF rw L ^ z K Lf 1EHU3 HEELW R<> i 166'lFPQRSSTAI il 8000 | 1757il AVAGTITVV iL3. 000 | 8611 GVPPLTSNV il 1. 0001 |il SPTSDYVKI il639|l IAVDNDTGM jL 3000 1 1765|1 VVVIFITAV il 1 000 1 2. 400 1 0-0-1 IVNPVNDTV I 1. 000 1 gE3<iw ; 1EI KVTINVVDV IE 1t v imo, Ir 0|1 VPSIDIRYI il 8000 0 lEo6Jt LPLDNTFVA |1 2. 000 1 11423ll IQLTKVSAM'L1. 00t } r i = Awa i-n 1E, 1 TPLNSKHHI i [H ii946 1 SVHTRPVGI | | L ; Oõ1 F ? Loo RRLIHL . 000 00- -IEP : F- 292 ; VPSIDIRYI'8. 000 : 906 ? LPLDNTFVA A2. 000, ? 423 IQLTKVSAM ! 1. 000 894TPLNSKHH1 : 8. 000, ; :, 946, SVHTRPVGI 2. 000, 267 VLASDGGLM 1. 000 w [wì 1EM3X 27 mo 1= r 417. LENNSPGIQL il 6. 000 | 1175S9VMVAGT1 1L2. 000 1 3 888 ; FQIQPETPL. 6 000 ; 287 r D, VNDNVPSI _ 2. 000 y , 273 GLMPARAMV 0. 900 FLo--3-, Lp-vT-QsK 2=o o o 417 ; ENNSPGIQL ; 6. OOOy, ; 754 LVAAVAGTI , 2. 000 ; õç IRmLXOOOX | Table XIX-109P1D4v. 1-B7 01 R ~-__ I w> _ 1 10 mers ll Sr [vppu [ : ! ! [GNRVT 4. 000 .. iyA ! LPDE ! JL. 2. 000J) position is specified, the L., NN. p-G, 6=o o 7, jEL _YqT7 [L9 1, F2 : G 2. position is specified, the length of peptide is 10 amino acids, and the end position for acids, and the end position for 460 i GMLTVVKKL 4 000'591 VSRSSSAKV 2 000 position plus nine. [. I __. . 274y, LMPARAM, VL. 4. 000 882, ASPQPAFQI.. 1. 800. Subsequence Score lRrSNCSYELVL'| 4. 000 0 i| MVAGTITV ¢---21 f -, 223 KIHFSFSNL 4. 000 [3 : 800 [APVGTSVTQL - ,... 36 ; STKEYAIKL ; 4. 000 : 272 : GGLMPARAM 1. 500'' 3 200. 00 ; 773 VVRCrQAPHL r v'vi v = 1775 rrnA Du 54 ILPDEIFRL : 4. 000. 678 KCDVTDLGL 1. 200 j 615, VPPSnCSYEL 80. 000' ; 420 GIQLTKV 1. 200 F4'L6 NAIDN-L, 8 000 Ir420 we. R<LH r4w 1 ; 4il KIRFLIEDI Li°°°, 110511DPDVGINGV} L1. 200 | |349jlRPVFsNQFLL, @0000il [6 [ESti iXLPDSLFSW't 1. 200' 1 [<1HI L ^ g ; a M s w 1 O-mers B3501-9-mers I B3501-9-mers ,..... _. _ Each peptide is a portion of Each peptide is a portion of Each peptide is a portion of SEQ ID NO : 3 ; each start SEQ ID NO : 3 ; each start SEQ ID NO : 3 ; each start position is specified, the position is specified, the length of peptide is 10 amino length of peptide is 9 amino length of peptide is 9 amino acids, and the end position for acids, and the end position for j acids, and the end position for each peptide is the start each peptide is the start each peptide is the start position plus nine. position plus eight. Subsqaence ° Score °. ........ L....... VA" KP : PLNQS [0. (O 138 : MPQLiVQKEL 80 0 . OQQ ! Ignn Ah i on nnn = =. ~ ì == v 383 : KPPLnQSAML 80w000 q. 5' SPTSDYVKI : 12. 000'267 VLASDGGLM : 3. 000 j I ? q 745 SPTSdYVKIL 80. OOOM iSiEw Xj_VPSIDIRYt 415jj IPENNSPGI ja, < 446 ; GPDApPEFSL 36. 000 639 IAVDNDTGM 12. 000 i 64 KIRFLIEDI 2 400 C_ VTTIE_F 7,, 4 ?, Fp ! Tsiff-F,, . ooo-i I qO_ "842 ; RVTLdLPIDL 20000 921 CSSSSSDPY. 10. 000 102 AAVDPDVGI 2. 400 _. . . : (... H., ! _. r | I __A ~ __., _0.. __ « ; . L. 7, i SPIDIEEmL20, 000 Xj ilElwlwi WiLEE n nnn i í= vo r _. < 5,, LVYKtGDVPL, 20 000, 732 ; APVTPNTEI, y w 8. 000 '742. DVSSPTSDY 2 0 0 481 ; LAKDnGVPPL 12. 000 : 7g APLFPATVI --8--000 71 DINDNAPLF 2. 000 leUlJlLr\rsunsvrrLJi lL. UUU ; 1176íl APLFPATVI-I 8. 000 171 il DINDNAPLF il 2. 000 f ir | | if » fw. _JW 535mAILPdulFRL 112. 000 1 1jl86igjE 8 000'356iiHi-Aãvj 2. 000 f l f l f l [E _ } > =ww » 377'LAADaGKPPL.,. 12 000, 166 FPQRSSTAI : 8. 000 w 843iLDLPIDL 2. 000 a B3501-9-mers IL3 ? i Ly-s-N-1RL 'SV > Vf V H ''01'J ! l j [435J [SGP ! r2 S B3501-9-mers i-f I iSl703fl FSVVIVNLF ii'5000 i I272 ; IGGLMPARAM il Each pepbde is a pûrtiûn ûf 11 lt _, ~ _-,. _ » position is specified, the' 906 LPLDNTFVA, 4 00 616 PPSNCSYEL 2. 000, length of peptide is 9 amino - acids, and the end position for , 630 ; NPGTVVFQV ; 4. 000 714 ESVTNATLI ; 2000, Ij each peptide is the start il ij626} ijl69j <, ju0-6 . ..., _ l. _. .... v.. " i position plus eight", f £ =-' 610,. KPVFIVPPS 4. 000,.....,. 384,, PPLNQSAML" ; 2 000,..... Posw ^Subsequence ^ Score.. 593 RSSSAKVTI y 4. OOO, TT 502 DQNDNSPVF 2000 40 IPRDEHCFY 360. 000 ; - ; 420 SPGIQLTKV ; 4. 000 531 j LITVTDPDY : 2. 000 i.......... . .......... ... ... I.......... _.... __.. _.... : 383 KPPLNQSA, 80. 000,, 4-49- APPEF-SLD-C 4. 000 423 I-QLTKVSAM : 2. 000 523 LPRHGTVGL 60-.-000 X I fl Jl il. I ff_ fl 11. f 1,,., LPIDLEEQT. [ 16.. TGMNAEVRY : 5ri [_.. 2. 000 [17] F§ KNkl7 E6Q. Eoo-7j --.. . _ :..... . . 950, RPVGIQVSN 4 00 445 LGPDAPPEF, 2 0 9-7Fs-pV F T-H N F4 O-P 0 'ro] ! pARAMVLV) 4 : 000 1 i 688)) RVLVKANDL !'200 ! 275 MPARAMVLV 4. 000 ', 68 RVLVKANDL : 2. 000 302, NPVNDTVVL'30000., IF391 fFPYFSNQFL 40. 000 2775 FM-PRM-VLV 4. 000 2. 000 iñ<j ;'iEri<0 3. 000 ïj 39 jf FPATVIN [S. o-õõX ia74ilB1i onnnn sil, lFil ~e <"_m iVQsF !"IoM" tBREEKDTY'Ll800" w rv ; r fSI = =, j.. o. = ....... _.,. fW9 [El tã fwrH fiWfltiñãii-Ng-0 oogl Table XX-109P1 D4v. 1 Table XXI-109P1 D4v. 1 Table XXI-109P1 D4v. 1- B3501-9-mers B3501-10-me s LB3501-1 0-mers Each peptide is a portion of Each peptide is a portion of Each peptide is a portion of SEQ ID NO : 3 ; each start SEQ ID NO : 3 ; each start SEQ ID NO : 3 ; each start position is specified, the position is specified, the position is specified, the length of peptide is 9 amino length of peptide is 9 amino length of peptide is 9 amino acids, and the end position for acids, and the end position acids, and the end position each peptide is the start for each peptide is the start for each peptide is the start position plus eight. position plus eight. position plus eight. S Subsequence l| Score i llXI APVGtSVTQL iE w| VPVSvHTRPV {H [.. KPVFiVPPSN- . ji, 0KVKDENDNA|| 1. 800 j ~jEõ õõ W11 RPVGiQVSNT 11@ooo7 , 610 KPVFiVPPSN 4. 000' ; | 59e SAKVTINVV 1. 800'',, 1 g VPPLtSNVTV} w ..... . . ; 596 SAKVTINVV 1. 00 ;--_ ; 487 VPPLtSNVTV j 4. 000 837 DSDGNRVTL Y1. 500 : 166 FPQRsSTAIL ' 5 626 LPSTnPGTVV 4. 000, Iji [ET H W < H "95 NSKYTLPAA4 1. 500 I 20. 00' 906 LPLDnTFVAG : 4.000 X _,, 1 _< _, _i O % igg 1vs m pC = k 308 WLSENIPL 1. 500'481 LAKDnGVPPL, 8. 00 744 SSPTsDYVKI 3. OOOE Aw w_ r ìt O | u {rww !,., < l ERi lUI <RooX 1189711 NSKHhllQEL ; oUUX < K wtwww= lg baw www ww iMiX t H Rr i 468ilLDREKEDKY1| 1. 200 i D ; 1 7ioE 139 ! | GlPRdEHCFY ISõoo == = AW W =v a W _ ? W W v : W 1| 817 l SPKNILLNFV u A I sW5 [am ; lwwUwwj W e E llS Eal IrS iLDcRTGML l XL+ LDPjDVGiNGvJ'"i. 200j =======-==J-698 L9EPS [FSVJ400 243 NATTGLITI : 1 200'453N FSLDcRTGML F 10. 00 795 ATPN ENRQM 3 000 105 DPDVGINGV, 1. 200 ° -------- ; 698 QPDSIFSVVI 2. 400 434 ; DSGPnAKINY 0, 2 FSLDCRTGML '. . _. _. _... Table XXI-109Pl D4v. I-FS SnL SNI 3B3501-10-mers 506 NSPVfTHNEY s 0 il Each peptide is a portion of position is specified, the. 1 IiX,.-XF~. pATvlNlsl 3 1 _N _ GLDV. SEQ ID NO : 3 ; each start acids, and the end position i ; 12 EVPLIrIEEDT, 2. 000 630 NPGTvVFQVI 8, 000 613"FIVPpSNCSY 2-. 000 for each peptide is the start,---- length of peptide is 9 amino IPLNTKIALI | ; ibsequence Fl |, wiL dENDDF 1 iii0-7il swp-wGiwq. LTKwwv-s-| .. '_ _ a.. . _ 368 STKE AIKLL 6-. 000 for each peptide is the start LiY 4E : I |847i| LPIDIEEQTM i|l2o0o'0t t 1ß3wrwV-SVHwtRPVGl li [ [f'^"^'< 377 i LAADaGKPPL 6. 000 I I _,. _ 530..., GLITvTDPDY p 2^000 Hoo iiW S, °VFtH, NêYN'i|2. 000zi 40. 00 ; 132 TPEGdKMPQL, 6. 0004, 50, 7E, SPVFtHNE N 2. 0 927 DPYSvSDCGY i r-- 3E77 I DaG IF -'- _* _ --- E 91 ; NSAInSKYTL 5. 000, ; ; I_, _. W, _ I... i 275 MPARaMVLVN 2. 000, 0 i5Y 2i QLTKVSAM 2. 000 : ! 140. 001 -. : -f 936 YPVTtFEVPV 4. 000 f 4361 GPNAkINYLL'o OOi"C. °' w ...., 302 NPVNdTVVLS : 2. OOOk < =1< t l9Fl, 12. 000 ; 4 000 (135,'MQLiVQKELJ (, ° L (_. _.. I . T G41) S X Dkl t nGA B3501-10-mers A1-10-mers A1-10-mers Each peptide is a portion of Each peptide is a portion of Each peptide is a portion of SEQ ID NO : 3 SEQ ID NO : 3 ; each start SEQ ID NO : 3 ; each start position is specified, the position is specified, the length position is specified, the length length of peptide is 9 amino of peptide is 10 amino acids, of peptide is 10 amino acids, acids, and the end position and the end position for each and the end position for each for each peptide is the start peptide is the start position plus peptide is the start position plus posnon plus eighi nine. ; nine . __ 107, DVGInGVQNY 2. 0, 00 00 i 467 KLDReKEDKY, 2 500 l 31 APHLkAAQKN E WI DLEEqTMGKY 1 ljH, HAV2N TGMNA 1w 850 DLEEqTMGKY ^ 850 L DLEEQTMGKY 1wE HwiM W S w LT-e ! PVS 1 2 [9-L70 TGElfrTGAR F2. ? 5, == 34 DSGPNAKINIY ii-O-OO-l 310 LSENIPLNTK 41 o I 1E1 VSDCgYPVTT { e ; __=_ =_ _t _ J 199H f _ E ; r < w 363 YLDYeSTKEY E gELTsNVTVF X it L. I<I t 31X H.,, It<r v v i 27. 00 1310 LSENIPLNTK VSDC YPVTT 9 ..... [''- .. : : ". . g_ W I < 1 ii tíl6001 KVED9GFpQR I v v I Iñ<|H VTDLGLHRVL j 1. Ql L6, [ : DT [L8 I L, : 584. KAEDgGRVSR 8 00 53 ; AILPdEIFRL : 1 500 ; : 181, j, DTNDnHPVFK a 1 000, 307 ! TWLsENIPL 1 500,-269 ASDGgLMPAR 5. 00 £ 378 ; AADAgKPPLN i 1. OOOw ISFDREKQES 18. 00.. ETEleVSIPE 2 1. 5002 15. 00, DAGKPPLN 269 ASDGGLMPAR LAA ,.... ..". 301,, VNPVnDTVVL : 1. 500e '2. 50' 126 GLDViETPEG 1. 000. f 3 07. 1 GLDVIETPE 1. 9 (l ll 38 llAGIPrDEHCF. |1. 5001 llFiõoõl ig| RTGMITVVKK l1. 0001 7ìl TlD<''TR R i S' XBLXII ilU. Vt"o I 1HE 0 AGIPRDEHCF 1. 500 458FRTGM] TVVKK 1. 000 10000 iXl RlEEdTGEIFjEX} lgjL VSSPt VCiH'IEI VETpE_DKM | '5F571 [TIDSQTGVIR 692 KANDIGQPDS'1. 200 290.... DNVPsIDIRY 6,. 250,., f 827 TIEEtKADDV v0. 900 (..... .. I I, 16 T RIEEdTGEfF i 1. 200 743 VSSPtSDYVK 6. 000, ; 129., VIETpEGDKM 0 900 ; if 573ilREKQeSYTlt w igOiL NSPVfTHNEY fflw itoo, =rn l_-_ __ _ _ ~ _. _. 573 e REKQeSYTFY ; 1. 200a 613, FIVPpSNCSY ; 5. 000, ; 506, _NSPVfiTHNEY 0 750 729, T STEApVTPNT 4. 500 f. 228, FSNLvSNIAR 0 750,, ; i Mb X tO9P1Dl 648jwfv If, 288tf, VNDNvPSDI _ffi O. 625, A1, 10- ers . _ i, 88 IPENsAINSK 4. 500 ; . 606., VNDNkPVFIV 0, 625 ; 747, TSDYvKILVA 3. 750 _ . .. . __ Each peptide is a portion of I WE% fW tXrENDNãPVFTQ i jrO. 625p il SEQ ID NO : 3 ; each start. 1. ro=r r _.. _. i_, 4_ _ _. R position is specified, the tength ! 418 NNSPgiQLTK j Z500 ! JJ72J ! NDNaPLFPAj 0. 625) ij of peptideis10aminoacids, 1 tEGiL ELDReEKDTY ! ; rW ! and the end position for each !-n-T AE-\m\/ T--= !--- :----"'-"- and the end position for each nine. 549 ILDEnDDFTI 2. 500' g14 ACDSiSKCSS 0. 500 454--S-LDCrTGMLT 2. 500 !-"Subsequence"Score' ! =JSLJj ! EE !) [ 2. 500 _ llnZ q 11 1 S=<r1 1v1 osi i ? 785j VTDVNDNVPS It Table IX-109P1D4v. 1-. Each peptide is a portion of Table Vlll-109P1D4v. 2- Al-10-mers SEQ ID NO : 5 ; each start I N'terminal-A1-9-mers position is specified, the length ( of peptide is 9 amino acids, and SEQ ID NO : 3 ; each start SEQ ID N0 : 5 ; each start the end position for each position is specified, the length £ = position is specified, the length the end position for each eight. and the end position for each the end position for each nine. -'= eighh. 12 ___-eight. nine. FRTSTI-EICS [ : 07 ¢1217|1 DlGEnAKIHF i û. 500. rFrOi 1 16 X LCGLIQQTV'I 0. 010 i : _, PTDSRTSTI 0. 1 5 _. 53,. AILPdEIFRL 0. 500 ; 4 14 STIEICSEI 0. 025 J Q. _, IQIFQVLCG 0 007^, ? - PTDSRTSTI 0. 125 2STNPgTWFQ w 5 ß HTRPTDSRT me m FQVLCGLIQ t 0. 007 t -# l l ¢ S g wv = : m _ t v. = L _ r T . l... . ....... m < = wi s L v > n 01151tt EKDTyVMKVK 1°5°°''HS ht 6 1t QWVLIQIFQ, it 0. 003 t IFRL 0. 500 lK301 GPNA_ L5 0 0-2 F---L-I F-1RQ-LIQ ! ', 0. 003 VSVHTRPTD 0. 003 YV E2 m m r of f ; 020HLMPaRAMVL't0. 500 S tHoF tlAlm ILK ¢rrrv vvrw ll889tl PeTPUN 0. 500 ; PVSVHTRPT"0001 ? 3, _, TVTSVPGMD., 0. 001 12 FQVL G 461 MLTVvKKLDR'0. 500 = 1 TSTIEIC 0. 001", j A 12 IFQVLCGLI, y ; 0. 001 y l rv m s El TI 500y. IIDQnDNSPV 0. 500' i g, TDSRTSTIE j 0. 000 .. 28w, ., PMDLLSGT, j 0, 000 ( DAPPeFSLDCj [o-.... - E20JQQSVp] 00 .. . .. . ... . : 140. QLIVqKELDR 0. 000 Z ... _,.. i..., .. _ : HTabIeVlll-109P1D4v. 2- i|1401L QLIVqKELDR 1°5°° gI TableVIII-109P1D4v. 2-ITi 0. 500 .. : ., z 11 Each peptide is a portion of fl,,,.,, A | 9-mers 1 ..,.. .. . _. I SEQ ID NO : 5 ; each start Each peptide is a portion of SEQ (L LliYrYX2 ! position is specified, the length ID NO : 7 ; each start position is j920j KCSSsSSDPY ! j0. 5M j of peptide is 9 amino acids, and specified, the length of peptide is 881 SASPqPAFQI, ,. 0. 500, i fhe end posifion for each 9 amino acids, and the end - peptide is the start position plus position for each peptide is the f 603, WDVnDNKPV 0. 500 ; eight. start position plus eight. , 26 TTGArIDREK4. 0. 500, _ ..... ; Pos ubseque e,, Score,, Pos, Subsequence Score, (-Q o FL5, [, KT-Y--7-E : 2 :. : 5 : 0 : VSIPENAPVG 0. 300 0050 F-,, IQSAMIFIKVK Fo-37o-C - I. ... 1. _...... ....... ___. 1 ? Z8J.... QAfdQKj) [00]"oj iQjYor" 712 VNESvTNATLy ; 0. 450. : 26 SVPGMDLLS 111 STFIPGLKK- 2 500 Z388j| QSAMIFIKVK jO VLIQiFQV r OEO 1 I 29l wrWl ! f8r'DSPD'ARHYKj [Q] 8'] [GUQQfs] [020"' ! - --.- ... 196 ;, VSIPeNAPVG.,. ; 0 300 ; 22 QTVTSVPGM 0 050 234 SAQASALCY 2 500H 388.' ; QSAMIFIKVK 0 300."7 ;, WVLIQIFQV 0. 050,. 29 !, WIHPQPQRK 2. 000 871. DSPDiARHYK,. 0300. : 18 GLIQQTVTS 0. 020 j 1 8 DPESTFIPG 1. 125 86 ISIPeNSAIN ! 0. 300 ' 9 LIQIFQVLG 0, 020'' 128 TVEEASDNC 0 900. ' 872"SPDLaRHYKS'0. 250 j f 7 VPGMDLLSG I 0. 013 120 :., AAEITVQPT 0. 900 ; LIQQTVTS 1. 125 wríw7 t=, iwr0013'11 i0li2Oi0M<r 5 VLIQIFQV 0. 010 62 SSDGGLGDH 0 750., F C'Terminal-A1-9-mers i -w--r , 33 15 30 VLCGLIQQT Z| 0010 ! Table VIII-109P1 D4v. 3 Tabie VIII-109P1 D4v. 3 Table VIII-109P1 D4v. 3 A1-9-mers-. li : e''s) j :'I' A1-9-mers I Al-9-mers ! _ Al-9-mers Each peptide is a portion of SEQ Each peptide is a portion of SEQ) Each peptide is a portion of SEQ ID NO : 7 ; each start position is) D NO : 7 ; each start position is ID NO : 7 ; each start position is specified, the length of peptide is specified, the length of peptide is specified, the length of peptide is 9 amino acids, and the end 9 amino acids, and the end 9 amino acids, and the end position for each peptide is the position for each peptide is the position for each peptide is the start position plus eight. B r r _. . C .. __ 3' ... . .. f... _ _ = S. ~ = z lt ^- SVHTRPPMK, 40400 , 77 = STSHGLPLG 0. 050 ', 190 IALCHSPPV ; 0. 020 1F ; STSHGLPLG ; E 0. 050 1'M0 {1 IALCHSPPV 11 0. 020 23 SALGYSPPL 0 020 j 00-50 0. 020 1. , r 1v3 Stv w 0. 050 i3 . wL. _... .. .... ..., _. . .. . .. . _.. .. w_ 3= i, 54, <1 |'Rl LCHSPPVTQ 3HõiC 33 3|RTEG GNSD. | 0225 3 WSL"L"AQ AISH i1 0050 11 3EI""LC"H SPPPIQ 31 0. 020 j 100 : RTEGDGNSD 0. 225 246 LAQAAAISH ; 0 05 : 204 LCHSPPPIQ 0 020 £. . y. w t... w. .. . _.. 110 : ESTFIPGLK 0-30-0---'1 0-050--l 0. 020 230 HSPPSAQAS : 0. 150 322 TFTPRQQAR"0. 050 185 RVTQTIALC 0 020 218 ;, HSPPLVQAT 0. 150 _, ,.. 83 PLGYPQEEY 0. 050 . 147. DACWMPASL OT020 177 : ASTQHHSPR : 0150 ; ! 282 GADGLCSVD, 0 050. f-.... t.. -. ,.- ;, ; _=~^, _,", 3, ~, __~ 3-----~-, 1 31 Al-9-mers 11 206 : NSPPPIQVS ; 0. 150 ! 10 TMKEWRSCT'0. 045' A1-9-mers 3, 170 ! iX E F 1 ~ Al-9-mers 0. F FP - (QV- lCVVq7q-T I Each peptide is a portion of peptide is 9 ; (t. ... _ 1 _ T... _ : t __ I . .. 9 i ids, and the end position ---_--..- for each peptide is the start ì|LVTQTIALCH il 0. 125 l 33t287} CSVDQGVQG3i3 0. 030 3 3aL position plus eight. ffii3 3 ç = 33, 3 L v 3 _ _ _~S, _9K. u31 0. 125 [C : Q : E qL I-QAd, Fj. L30 G 17L7 Ft s os i Subsequence 125-FLQ-VIA 0- ,, E-9 : 125 F-§ F--i. _30 F4-....'. FHPQPQSQRR 10. 250 W. ~3Ws 3 6 l Ws ~~3 i ll i< t [HLH3 iS-l YPQEEYFDR il 0. 125 im41i MSERLHPSD Iì 0. 027 l 1m1 PQSQRRVTF 1 [9-4 E ( ? G-2 IHPQPQSQ 0 oo ! iW| DHDAGSLTS il 0. 125 iì ildi. 3 j8i| IPLTTFTPR il| 0. 025 i il 6 | QPQSQRRVT -- ° 1 f.. I.... . .." p I _Qt25 2 T. [T QFLMS 5 ì _ 5~ _A______w_~ t=___. __ I. . _ ; : | I I....- 3,, jFG7iisl-E-EA ?-5 T FTp-pmE-v j o2-5 Q. 1S. Q. RRV. tF if3- i_=, ___ _ iVX_ li < 16 SCTPMKEST 0100 ; 105 GNSDPESTF Z 0. 025 i i ~ J =,... Zi, == '_ì , 307 ; RLHPSDDSI yY40. 1, 00 j 205, CHSPPPI, QV . 0. 025 'I, __. A1-10-mers E Lim v f w Zl A1-10-mers Each peptide is a portion of SEQ j ID NO : 9 ; each start position is F4T- 41 KVAGKSQRR ! 0. 100. TPMKEST M25 ! , , the iength ofpepMe is ! F, ! fled, the length of pepfide is -F. 975 10 amino acids, and the end Zi ; llHiiX i lilwr-0-0r. {positionforeachpeptideisthe 01 start position plus nine. Xl ESTTMEIWI °< 1150 11 VTFHLPEGS t 0025 I position for each peptide is the 295f GSATSQFYT i0. 075 215 mALHHSPPLV 0. 020 " WHPqPQSQR 1. 000 F76-'i TST§HGLP qO-7 TFTP-RQQA 0. 025 YT't 0. 075 2111 [L : HP VjE : §. L2 ( =3 1 1. 0=00 > ALCHSLS L D O2 T ble IX 10 P 4 4 Table XI 109P1 D4v. 4 Table XIV 109P1 D4v. 4 A1-10-mers A0201-10-mers ° Al101-9-mers H Each peptide is a portion of SEQ Each peptide is a portion of SEQ Each peptide is a portion of SEQ ID NO : 9 ; each start position is ID NO : 9 ; each start position is) D NO : 9 ; each start position is specified, the length of peptide is specified, the length of peptide is specified, the length of peptide is 9 10 amino acids, and the end 10 amino acids, and the end amino acids, and the end position position for each peptide is the position for each peptide is the for each peptide is the start ; start position plus nine. start position plus nine. !, ì position plus ei9ht. start position plus nine. start position plus nine. position plus eight. Subsequence lG°R 50H Subsequence t Scorei 1tõE Subsequence j Score Subsequence Score Subsequence Pos v s l l 5 2 HPQPqSQRRV 0. 025 1 7 1 QPQSqRRWF 0. 000. 4. HPQPQSQRR 0. 040 s =-h #-@ _ 1 QSQRrVTFHL 01 0M 11 4 li IHPQpQSQRR Sõoõl 11 3 ! iSlCõ i. 1wo i J 1 4 J [lHPQpQSQRR {{0. 00e 1Wl IWIHpQPQSQ AH 1<1 PQSQRRWF 3E 1 il ElWlhPQPQS 1'I 2 tWIHPQPQSQiL 0. 000'. 0 Aq 9 mQr IF _qq§Q 0. 00. Table Xil-i 09PI D4v, 4 q-f RC\g--H 2 IWIHPQPQSQ 8 : Each peptide is a portion of SEQ : -IW-I-HPQPQS 0-. 000 : 11--] LQPQsQRRYIJ 0. 0=0 0 F-5- [P-9 ( : S-V, [-. 00=0 specified, the length of peptide is 9 ; QPQSQRRVT 0. 000 : rs} t| amino acids, and the end position j F T i l-. "°"""'""position plus eight. Table XV-109P1D4v 4 n Each peptide is a portion of SEQ - £ A1101-10-mers position plus eight. .,,..,.. ^11- ! r-I t1 ac pep X e Is a po lon o ìl p 1.. _w. _ _.,... _, ; Each peptide is a portion of SEQ' specified, the length of peptide is 9 q. HPQPQSQRR I 0 060 : amino acids, and the end position il or eac pep I e IS e s a 31 S I 10 amino acids, and íhe end. 1 , 10 amino acids, and the end for each peptide is the start o,,-,, * 10 amino _.. and the end Pos Subsequence Score WINPQPQSQ 0 003a start position plus nine, 0. 0061 _ w WIHPQPQSQ, 0 009y. 6 QPQSQRRVT 0. 000 3 WIHPqPQSQR 0 080 ; IL 8 ! l QSQRRVTFH iL0. 006|1} L 1 1 IWIHPQPQS A IHPQpQSQRR t PQPQSQR V-1 Score, PSQRRVTFH Table X] l O9Pl D4v, 4 10 s : : e I ..- i13 : X1FFE I E <1 lmit HPQPqSQRRV jEooll C IHPQPQSQR ; 0. 000 ; 4 Table Xlll-909P1 D4v. 4 j f, 9 QSQRrVTFHL joui' .. - # i.. A3-10- ers --- I.. ... IW (HPQPQS 0 000"1 EIWIhPQPQS 0. 000 ; Each peptide is a portionof 8EQ, }--- ---- ; HPQPQSQRR _ 0, 000 ID N0 : 9 ; each start position is 3 HPQPqSQRRV E0. 000 : specified, the length of IWIHPQPQSQ Q.. 000 Table XI-109Pl D4v. 4 10 amino acids, and the end PQPQSQR . _ start position plus nine. WI Each peptideisaportionofSEQ 11 1 = = 1 TabeW ID NO : 9 ; each start position is f L A24-9-mers Xi Le or I... __.., . q.. _. _ 10 amino acids, and the end Each peptide is a portion of SEQ position for each peptide is the 7 1 QPQSqRRVTF 110 020 {1 il ID NO : 9 ; each start position is --, start position plus nine. specified, the length of peptide is 9 QSQRrVTFHL-, l 0. 0 ; for each peptide is the start j EIWIHPQPQS 0. 0091 amino acids, and the end position .". WIHPqPQSQR ; 0. 009, ; 8 PQSQrRVTFN 0 002'Pos Subse uence ScoreV reac pepl els esa for each peptide is the start L1. sI ElWlhPQPQS'|0. 00611 Sl 5 itHpQpqsQRRv flo, ooo I,, 1 7 il PQSQRRVTF 10. 200, i , <L HPQPqSQRRV < 1 6 J| PQPQsQRRVTS 6. LQPQSQRRVT uH11 8 iL PqQrRVTFH =2 LMPQ-PCLS-Q l 0. 000 IWIHPQPQS ; 0. 150 ;, 10. 00 1, 1 ! F : 71'.. HPQPQSQR ELP ! YI.. i ! . 4, J IBPOPOSORR WhC m SA Table XVI-109P1 D4v. 4. . _ v _ : Table XXI-109P1 D4v. 4 A24-9-mers ble XIX-109PI D4v. 4 B35101-10-mers H n7 n'g Each peptide is a portion of Each peptide is a portion of SEQ ID NO : 9 ; each start position is Each peptide is a portion of SEQ ID NO : 9 ; each start position is specified, the length of peptide is 9) iD NO : 9 ; each start position is specified, the length of peptide is amino acids, and the end position. specified, the length of peptide is 9 amino acids, and the end for each peptide is the start 10 amino acids, and the end position for each peptide is the x start position plus nine. 1<> 1X Ij ; ; Pos Xjr Subsequence NrscOre | 8 QSQRRVTFH 0. 05 : P°. . Subsequence Score.,.. 5 HPQP SQIIV 4. 000 Subsequence Score ! PQPQSQ QSQRrVTFHE'F4-. 0-00-1 w~ » e_|_u » J I : § I r g t _ _ -oR §1 5 ßlHPQPqSQRRVll 4. 000L W19 H1 I LPQSQRRVTFH 2. 00-1 Table XVII-109P1 D4v. 4 _ WHP4PQSQR j Orn015 IWIHpQPQSQ y 0. 001 ; A24-10-mers g WHWi<E 1 8-w ; EE i ~ 7 7 ; F Each peptide is a portion of SEQ } m i o s L1 6 I PQPQsQRRV tLO 01t CC [wE i v ; wimE ID NO : 9 ; each start position i's...... specified, the length of peptide is Table VIII-109P1D4v 5 10 amino acids, and the end IHPQpQSQRR 0^001w A1-9-mers position for each peptide is the Each peptide is a portion of SEQ start position plus nine. Table XX 109P1 D4v 4 Pos Subse uence ; Score B3501 9 mers specified, the length of peptide is 9 amino acids, and the end 9 QSQRrVTFHL 8. 400 1 position for each peptide is the mr+ j ID NO : 9 ; each start position is start position plus eight. start position plus eight. I specified, the length of peptide is 9 ! Iw. . . _. I. _.. .. : amino acids, and the end position : I. .- Scores position plus eight. Q P. O 181 TRVTF 0, 0503 : Pos. ,. Subsequence Score, i Score' ; QPQSQRRVT 2 000 ; 9.-oLo , IHPQpQSQRR 0. 002 < .. HPQPQSQRR 0. 200 : 4 _PVSVHTRPS 0. 001 : QPQS _ . _... , QSQRRVTFH W 0 050W .. , TRPSQRRVT 0., 001. TTable XVIII-109P1D4v. 4 T ' 5 _ ! PQPQSQRRV, 0 020 : ---g---PSQRR/1'FH 0 000 [ B7-9-mers 1 IWIHPQPQS 0 010 ; - -. w. . __ I. _.... _ : ll B7-9-mers 91 s<<rõfõwO-I Each peptide is a portion of SEQ ID NO : 9 ; each start position is ; A1-10 mers specified, the length of peptide is 9 _LHPQPQSQR L71 Al-10-mers il amino acids, and the end position | amino acids, and the end position for each peptide is the start B3501-10-mers specified, the length of peptide is 10 amino acids, and the end position for each peptide is the ID NO : 9 ; each start position is start position plus nine 11 specifed, the length of peptide is : ! 4 HPQPQSQRR 0. 200 Pos Subse uence Score I LioLo specified, the length of pbptide is : start position plus nine. position for each peptide is the , QSQRRVTFH 0. 010 start position plus eight -q.-- ; -SVHTrPSQRR, 0. 100 .,,.,.-I i Pos | Subsequence ! 2 WIHPQPQSQ 0 010'j 6 HTRPsQRRV. p, 025' = _ . _. _ .-- ii 7 il QPQSqRRVTF lltUUUil I. _ ll= _ T = ==. il= ==wi _ I _7-TRPSqRRVTF 0. 010 003 7 [ ! QSRRVF iml 11 ç i, BtsBtrV""il v. vuv il 11. § il\ln\/X^ | lorn. ^ll. ^., ^, ^^, h ; CIHPQPQSQR 0. 002 T VPVSvHTRPS 0. 003. Table X-109P1D4v. 5 TabieX)-109P1D4v. 5) Tab) eXV-109P1D4v. 5 j A1-10-mers i, I A0201-10-mers {1 A1101-10-mers l Each peptide is a portion of SEQ Each peptide is a portion of SEQ Each peptide is a portion of SEQ j ID NO : 11 ; each start position is ID NO : 11 ; each start position is ! D NO : 11 ; each start position is specified, the length of peptide is specified, the length of peptide is specified, the length of peptide is 10 amino acids, and the end 10 amino acids, and the end 10 amino acids, and the end ; position for each peptide is the position for each peptide is the position for each peptide is the } start position plus nine.. $ start position plus nine. l start position pius nine. v = s art position plus nine. ! RPSQrRVTFH'0. 003 y f 6 HTRPsQFRVT j 0. 000' ; 4 I SVHTrPSQIR 0. 400 ; core PVSVhTRPS w0. 002 : TRPSqRRVTF ! 0 000'., VSVHtRPSQR 0. 006 RVT 2 l [PVSVhTRP-S i . uuz II \/utD OwNDD {l An a mGrO 3 S A3-9-mers Each peptide is a portion of SEQ OO V : l ID NO : 11 ; each start position is HTRPSQRRVT 'specified, the length of peptide is 9 : . _QRrVTFHL 0000 ; ^Table X-109P1D4v. 5 amino acids and the end posifion : VPVSvHTRPS 0. 000 ; A0201-9-mers f r each peptide is the start Each peptide is a portion of SEQ position plus ei [ : 5 VHTRPSQRRV ID NO : 11 ; each start position is specified, the length of peptide is 91 Lf-0 ! 21 Subsequence Score , Table XVI-109P9 D4v 5 amino acids, and the end position} oJõS'I Table XVI-109P1D4vi5 ll for each peptide is the start 7 RPSQRRVTF, = 0 020. ° Il position plus eight. i L _ w L'__. 2 [a 2 pti s a pon SeQ n I RPSQRRVTF 0. 0201 Pos, Subsequence Score ; 5,NTRPSQRRV specified, the length of peptide is 9 s SVHTRPSQR : 0. 001"'s-M-... I 0 002 ; amino acids, and the end position for 8 PSQRRVTFH 3 0 000 i each e TRPSQRRV 0. 000 -w----°--- p ptide is the start position plus i X i H s S I0 0 0 0 1 t e i g h t J 1 ' 2 VSVHTRPSQ . 0 000 : ; eighty hot } <1 PVSVHTRPS ! l Subsequence. Eí ; 2 VSVHTRPSQ v ; 0. 000 ; -.--. __.. ... _. _.. C ..... ° '6 I TRPSQRRVT 0 000 : Score _§yysquence VSVHTRPSQ 0. 000 ' Table XIV-109P1 D4v. 5 ====== !.--. J'lU"--- ! r VSVHTRPSQ ! 0. 015 t} IDNO : 11 ; eachstartpositionis 1 i VSVHTRPS ° o |l 4. 0 0 LqV-TFH 2 0. 000 ll TableXI-109P1D4v. 5 ll 3gspecified, thelengthofpeptideis9tl 1 3 Jl SVHTRPSQR. 1 0. 0a10 amino acids, and the end osition f A0201-10-mers p 8 PSQRRVTFH 0 002 j for each peptide is the start Each peptide is a portion of SEQ : positio pplus eight., . 4.,., HTRPSQRR, y. 0. 001" position plus eight. ID NO : 11 ; each start position is il 10 amino acids, and the end l l<iiQFII ll a e-v. ; l A24-10-mers' position for each peptide is the,". W-------- I 3 VSVHtRPSQR (0. 030 : ''"" " start position plus nine--, Each peptide is a portion of SEQ : A24-1 0-mers position for each peptide is the sv I I. T I _ c 1 9 I PSQRrVTFHL. 10. 0181'1 11 10aminoacids andtheend i 9 (.. pSrVTFHL 0 001 ; Subsequence Score ! c1 mi HTRPsQRRVT i I startpositionplusnine. II II 8 1 RPSQrRVTFH iL0 00611 F ~----9o-'I i 4w. ___. _->--í O. OOOil ivl Subsequence 77, Scoreil 4'I SVHTrPSQRR, 1 0. 001 il F w 1 VPVSvNTRPS 0. 000 :. W w !,...., wVPVSvHTRPS,. 0 000 : wPSQRrVTFHL 0 40 ; 7<o <SqRR TF 1X0 1 VSVHtRPSQR 0. 000 i !---_- wL .. °...., fCww _ = °-w- iE : , HTRPSQ 9 : 00 : : HTRPsQRRVT 0. 120I 4v. 5 Each peptide is a portion of SEQ ID NO : 11 ; each start position is specified, the length of peptide is 9, Each peptide is a portion of SEQ Each peptide is a portion of SEQ ID' I D NO : 11 ; each start position is NO : 11 ; each start position is specified, the length of peptide is specified, the length of peptide is 10 j for each peptide is the start 10 amino acids, and the end amino acids, and the end position fo position plus eig position for each peptide is the each peptide is the start position plus jilPos HSore ; 11, start, position plus nine. nine. v c = I.. _ _. iv =1 i Pos i Subsequence jS ii 3 il SVHTRPTDS ji 0 010 i RPSQrRVTFH 0. 020, TRPSqRfV'fF 0. 003 VSVHTf ; PTD' 0 0 VSVHtRPSQR : 0. 015 i 1 Hii Fi w SVHTrPSQRR j i TableXX-109PlD4v. 5 j 1 4 il VHTRPTDSR lioF I..... .. _ _...., : : VHTRPTD R 0. 001., , 83501-9-mers 5 VHTRpSQRRV I 0. 010 L-5---jL-yT RV 1, Each peptide is a portion of SEQ 2 j P/52 htRPS) O 001 ID I 40 : 11, each start position is i. Table IX-1 O9P1 D4v. 6 i specified, the length ofi peptide is 9 C'terminal A1-10 mers f -l S 9 l Table XVIII-109P1 D4v. 5 amino acids, and the end position ! Each peptide is a portion of SEQ ID B7-9-mers for each peptide is the start NO : 13 ; each start position is position plus eight. specified, the length of peptide is 10 i siti n lus eight. specified, the length of peptide is 10 ID NO : 11 ; each start position is Pos., Subsequen, ce Score : ; ; ; specified, the length of peptide is ! s 9 RPSQRRVTF amino acids, and the end position g HTRPSQRRV 0--. 6-00- nine. for each peptide is the start i .-. ----. . Pos, Subsequence Score, Subsequence Score for each peptide is the start f Pos, Subsequence Scorem. 3 TRPSQRRVT 0, 010. N y YVSVHtRPTDS ; 0. 015 HTRPSQRRV ; 2. 000 f PVSVHTRPS, y' 0 010 ; í Subsequence 11 core, LRPS9yll-. PTDS SVHTRPSQR 0, 050, ; , PSQRRVTFH 0 005, ! H---TR TDSRT v 0. j.. 2, ; wVSVHTRPSQ 0. 015' ; VHTRPSQRR 0 001, : SVHTRPSQR 1 6 Ji TRPSQRRVT 11 0. 015'i n "1 PVSVHTRPS 0 010 ; Table XXl-109P1 D4v. 5 C'terminal A0201-9-mers B3501-1 0-mers Each peptide is a portion of SEQ ID VHTRPSQRR 0. 002 s, Each peptide is a portion of SEQ ID NO : 13 ; each start position is NO : 11 ; each start position is specified, the length of peptide is 9 specified, the length of peptide is 10 amino acids, and the end position for wim D amino acids, and the end position for each peptide is the start position pius) B7-10-mers each peptide is the start position plusi .... -- nme. _ ; Pos Subsequence Score j , Each peptide is a portion of SEQ ID -°---I _ . Each peptide is llamlno aclus, anu ule enu poslllon lorS NO : 11 ; each start position is VPVSvHTRPS 2. 000 , PVSVHTRPT 0. =O 3 amino acids and the end osition for each peptide is the start position plus£ .. SQRr VTFHL 0. 500 v. . HTRPTDSRT 0. 000, nine. '. RPSQrRVTFN,, 0. 400 VSVHTRPTD 0. 000 Pos Subsequence Score HTRPsQRRVT 0. 300, _ VHTRPTDSR 0. 000 nine. , _ 9, PSQRrVTFHL 0. 400 ; VSVHtRPSQR A0. 050. _ Table Xl-109P1D4v. 6 Sore 6_, VHTRTP§R 0. 000 . _. . _. 1. _.... _....,. _, VPVSVHTRPS-10 400------- _QLRY 0. 0 [5 J ["v'HTRpSQRRV 0. 020., 10 amino acids, and the end Each peptide is a portion of SEQ , WW,. jrwwwwwwwwsl, 1 11 II 5 I VHTRpSQRRV 10@020il El lO amino acids, and the end Zl TableVIII-109PlD4v. 6 | poslbonforeachpeptldelsthe il w C'terminal-A1-9-mers startposition plus nine ; __ w_. 2 PVSVhTRPSQ 0. 008 E. °J Subsequence j Score Tab) eX) V-109P1D4v. 6 TabfeXVtt-109P1 D4v. 6 VPVSvHTRPT ; 0. 017 C'terminal-A1101-9-mers C'terminal-A24-10-mers l v. l J L_ _ n z < wX l Each peptlde IS a portion of SEQ Each peptide is a portion of SEQ ID NO : 13 ; each start position is ID NO : 13 ; each start position is specified, the length of peptide is 9. specified, the length of peptide is 4 SVHTrPTDSR 0. 001 amino acids, and the end position. 10 amino acids, and the end w for each peptide is the start. pûSition for each peptide is the 2 PVSVhTkPTD, 0 000' '1. iL=w_ _. 11. _. 1. position plus eight. start position plus nine. c mn < +H. w plus eight. start position plus nine. C'terminal-A3-9-mers _. "PSHTtPT 0 000 _. VPVSvHTPT 0. 150 ; SVHTrPTDSR 0. 010 ; Each peptide is a portion of SEQ ID N0. 73 ; each start position is Tabie XV-109P1 D4v. 6 ! [rHTRpTDSRT'0. 010 l specified, the length of peptide is 9 C terminal-A910-10-mers j .. I 2 PVSVhTRPTD I O. Oû1 i Each peptide is a portion of SEQ ID for each peptide is the start NO : 13 ; each start position is position plus eight. Table XVIII-I 09PI D4v. 6 t Pos Subsequence jrScore amino acids, and the end position for' , : each peptide is the start position p (us Each peptide is a portion of SEQ ; L-O-OL, =ine. ID NO : 13 ; each start position is I A ìl \/LITDDTnOD il n nna I __ __ _ I i Lbs uece Score ted, the length of peptide is 9 m [Hw 7=l I I amino acids, and the end position, - -w- 4 SVHTrPTDSR'0. 400 7í ~iWl ìtttJ~,"_ 1 I lûr eaCtt pepllue IS t"e stalt V r U_i'LEUUu Ij<i+l 1t position plus eight. {t o PVSYHTRPT t u. OûO CT ; I << iamino acids, and the end position . y. . .... __.. _... _ [ . .. ., w. .... _. . _ . . 1, VPVSvHTRPT 0. 000 HTRPTDSRT 1. 000' Table XIII-109P1 D4v 6 ! -°u ;. 1 VNTRpTDSRT 0. 000 SVHTRPTDS 0. 100 C'terminal-A3-10-mers Each peptide is a portion of SEQ ; , pSVH, TRPT 0. 050 : ID NO : 13 ; eachstartpositionis 11 r die (1 9P1D4 specified, the length of peptide' 10 amino acids, and fhe end Each peptide is a portion of SEQ4 ; ' F ; I.. _.. _ : position for each peptide is the 2 ID NO : 13 ; each start position is S start posified, plus nine £ Table XIX-109P1 D4v 6 specified, the length of peptide is 9 Pos ubse uence Score amino acids, and the end position ; C'terminal-B7-10-mers for each peptide is the start 4 SVHTrPTDSR. 0. 600 position plus eight. ll il ID NO 13, each start position is l) LVSVHtRPTDSj) 000 p subsequence JfScore"specified, the iength of peptide is li 2 !, 1 PVSVhTRPTD i|Ml jaii ti= [10 amino acids, and the end -- : .., HTRPTDSRT 0. 120 ; '1 VPVSvHTRPT ; 0. 000 -r--position for each peptide is the il 1 JLVPVSvHTRPT ilO. OOOjI Ir r 71 lì... II ------W 3 SVHTRPTDS 0. 100 ; start osition lus nine. ; .. t...... .. .. j---------------. 1 PVSVHTRPT (0. 01o1 1 JLYSvHTRPTj 2. 000 Cn XRP rsm Xim +W Table XIV-109P1 D4v. 6 i"4 ? HTRPTDSR 0 001 ; SVHTrPTDSR 0075 : C'terminal-A1,01-9-mers i-- _ . 3 ; VSVHtRPTDS 0. 020 : Each peptide is a portion of SEQ .. _.. _w I . . . _ H ; #| IDNO : 13 ; eachstartpositionis ii tr I jiml WlEl ; s ecified, the len th of e tide is 9 C'terminal-A24-10-mers ! --- =2 Y , PVSVhTRPTD 0. 008 x 'amino acids, and the end position ; Each peptide is aportion of SEQ' for each peptide is the start 11 | ID NO : 13 ; each start position is position plus eight. ^Table XX-109P1 D4v. 6 position plus eight. Pos Subse uence'Score 10 amino acids, and the end''C'terminal-B3501-9-mers -- osition fior each e tide is the v 4 VHTRPTDSR 0. 004, p p p ; Each peptideis a portion of SEQ a startpositionplusnine ! 1 #1 IDNO 13 eachstartnositionis ìl s 9n o start position plus nine. ID NO : 13 ; each start position is Ir ir Sjl [1 amino acids, and the end position ! 1 v 1 3 11 VSVHtRPTDS i, O. 150, ìl z L '_1 » A | 3 VSVHtRPTDS' ; 0. 150I for each peptide is the start ; VSVHTRPTD ; 0. 000, position plus eight. ; I Pos I Subsequence tSre TabbV'09P1D48 =-- terminal-Al-9-mers ble X-1 09PI D4v. 6 -Each etide is a orfion of SEQ : Each peptide is a portion of SEQ ID NO : 13 ; each start position is < j VSVHTREI 0 050 1 ! specified, the length of peptide is 9J) D NO : 13 ; each start position is specified, the le s 9 : ID NO : 13 ; each start po 0 amino acids, and the end position specified, the length of peptide is , 'n fo''each peptide is the start 9 amino acids, and the end 4 VHTRPTDSR 0. 009' L position plus eight.. ! position for each peptide is the -@S = =e Z Table XXI 109PI D4v. 6 r Subsequence tiscorel Ta lUDe1D4V6 *= ; t Subsequence tH . . SDISSWRV, 000, ; Ie i ..... C terminal 83509-0-mers L C't-erminal-B35, 01-10-mers TYI i. 8571l j) D NO : 13 ; each start position is LVVRVNTTNC", I [p--" specified, the length of peptide is 1 MTVGFNSDI ILO. 361 10 amino acids, and the end position for each peptide is the , 13 VRVNTTNGH 0 001, ----- SubeRgnce i [co :- SDISSVVRV FL ? i _P P 20 CHKCLLSGT 0 000 :--- P=08- e 0. IC3 VPVSVHTRPT 3 VSVHtRPTDS : 0. 500 ", N' terminal-A1-10-mers 10 T, SSWRVNTT j 0. 112j 3 VSVHTRPTDS N'terminal-Al-10-mers SSVVRVNTT- x ID N0 : 13 ; each start position is 5 ; VHTRpTDSRi'. 0010 M. ISSWRVNT 0083, specified, the length of peptide i RPTD 10 amino acids, and the end position for each peptide is the t position plus nine. lI Table V111-109P1D4v. 6<1 i SVVRVNTTNt N'terminal-A1-9-mers T Pos Subsequence S Score Table VIII-109PID4v. 6 Each peptide is a portion of SEQ .. ! VSDIsSVVRV. 1. 500 ; ... 3. . GFNSDISS 0. 003 [' , TVGFNSDIS 0. 001 ID N0 : 13 ; each start position is 22 s KCLLsGTYIF Q 200 : [, §ubquence I Scorei I 14 RVNTTNCHK 0. 001 j specified, the length of peptide is 9 17 11 _I\TTTNCHK 10. 001 amino acids, and the end position NCHKCLLSG p s 19 NCHKCLLSG 0. 001 ; 5 osition lus ei ht. 18 TNCHKCLLS 0. 000 for each peptide is the start Pos Subse uence Score a" 20 CHKCLLSGT j 0 000 K'CLLJI. 025J IF5.-0-00 F_ 6- 0 = Eqoooj , A. 23 CLLSGTYIF 0. 200 ,, ry, '' MTVGfNSDIS 0 025. I I : L__,, [NTTNcH 13 LyVN7NCH I I, 73 :] Fq. : O : o CLLSGTYI 0. 2 1,. MTVGfN 25 16, NTTNCHKCL 0. 025, , g ISSVvRVNTT 0 015 a 18 _j|TNCHkCLLSG |HTI l| N'termlnal-AO201-10-rners íl [147 =6 L--D-I-s--s-Y-Y l Lo zu o, oj I..... _..,.. ... fl.,., w N'terminal-A0201-10-mers . :. ....., ..... .,. ., _ _Yt i Each pepfide is a portion of SEQ ID ! 17) TTNCHKCLL J0. 025J ! jiRVNTtNCHKC 0010'NO : 13 ; each start position is _j . 925 specified, the length of peptide is 10 ! I _ VGFNSDISS '0. 013 i 15 VNTTnCHKCL 0 003 : each peptide is the start position plus rrmS Ir°l Ir |VGFNsDISSV'll nine. nine. TN, CH.. K. C, L., LS," VGFNSDISSV ilo.-Lo , (.. .... 22., ; KGLLSGTYI 0. 010,'12, WRVnTTNCN 0. 001 : i 23 CLLSgTYiFA 151. 648 . __ . . _ TVGFNSDIS 0. 010-7 Subsequence, 9core I 19 NGNKCLLSG 0 005 s 7'SsVVRVN''0 0'I 4 RVNTtNCHKC. C0. 4. 35j 11 j SVVRvNTTNC"0. 435 NCHKC N 7F VGF I ... ...... n -------E--_. _ _ _ __ r.. I Table X1-109P1D4v. 6 l 1 Tabi 9P : > 6 N'terminal-A0201-10-mers N'terminal-A3-9-mers N'terminal-A3-10-mers ; 1 [ : : erminal-A0201-1 0-mers N'terminal-A3-9-mers N'terminal-A3-1 0-mers Each peptide is a portion of SEQ ID Each peptide is a portion of SEQ : : Each peptide is a portion of SEQ ; NO : 13 ; each start position is ID NO : 13 ; each start position is) ! D NO : 13 ; each start position is specified, the length of peptide is 10 specified, the length of peptide is 9 specified, the length of peptide is amino acids, and the end position for amino acids, and the end position 10 amino acids, and the end each peptide is the start position plus for each peptide is the start position for each peptide is the j nine. s position plus eight. ! start position plus nine J POS ìl Subsequence j Score I Los I Subsequence iR X Subsequence ilGi i [ : pisl Su66ence i Score I Pos Subsequence Sosegenc Score : 16-t NTTNCHKCLL 0. 297 l 21 J HKCLLSGTY iw < < rTiEiX im<E T v E 16 NTTNcHKGLL 0. 297, 1 H4CCLLSGTY". 0. 00 : 4 GFNSdISSVV 0. 009 vf < -s R @ = = L19 iLNCHKcLLsGT j 0. 112 ji l 9, ISSWRVNT I 0. 001 i ì 10 i _ SSWrVNTTN | 0. OOOl r-i.-. - JLP ! SSvYR Jj-Li J ! i-tL'HKCLLSGj [jlO Ej8. 1j CHkCLLSG" (0. 000) --JL-n'JSd'SS\ j 5 FNSDiSSW 0. 001 ! ! L-LJ ISDiSsVyRVN MOO) IL...... ^ í ~ J l HKCLIS E 0 : 2EO 5=EEN7-DLs-\Y-Lg-oo-l. 1 7=-1 OE6 : 0 : 7 TVGFnSDISS.,., 0. 007 ; mm 15, TTVNTTNCHKC 0 000 ! 21 !'HKCUSGTYi ! j 0. 003" 3) VGFNSDiSS i'0. 000 ! TaMe XiV-109P1 D4v. 6 .......... E 22 KCLLsGTYIF4 0, 003 13 VRVNT ' "1, 8"TNCHkCLLSG 0 001 8 DISSVVRVN 0 000 Each peptide is a portion of SEQ ID HKCLI.. 977 F NO : 13 ; each start position is specified, the length of peptide is 9 GHKCLLSGT ooo amino acids, and the end position for ' f each peptide is the start position plus -1'_t iCo l 1_ elght. Jl NSFISSVVR 0. 001' l, il,,, < _ = l _. __s ¢1 B AN I Pos j Subsequence 11 Score 11 N'terminalA3-10-mers, -- SSWRVNTTN 11-109PID4v. 6 1==1 |'L lí Ll A l S j. aclpeptluelsapolLIonolocw íl i=~~~~b^~-->1 Each peptide is a portion of SEQ ID N0 : 13 ; each start position is ; I __, , ___-w. r 13 i<< iI specified, the length of peptide is ; 3 CLLSGTYIF 0 012 10 amino acids, and the end 20 CHKCILSGTY ^, 0. 000, v 17 :'TTNCHKCLL 0. 010 position for each peptide is the.--- ,. :.. start position plus nine 22 r KCLLSGTYI. _, 0. 009 -in N'termlnal-A3-9-mers 11 ? -----| I , Each peptide is aportion of SEQ 23 CLLSgTYIFA 0 600 ; 16 NTTNCHKCL 0. 005 0. 600 Each IDNO : 13 ; eachstartpositionis 11 IrEvi3 [il LE EiC : : lWli ||specifed, the length of peptide is 911 ßH3H< W 0. 003 | ! amino acids, and the end position || foreachpeptideisthestart || 1 16'il NTTNcHKCLL i&. 030jl 11_12 31 VVRVNTTNC || 0. 002 |1 position plus eight. 11 SVVRvNTTNC 0. 030 ; 2 TVGFNSDIS'0, 002 i + __ _ = __ = __ _ _ __ I ì F __ _ _ _ S _ +_ __ J I Pos. Subsequence Score ! 14 f RVNTtNCHKC 0. 020i 19 NCHKCLLSG 0. 000 specified, the length of peptide is 9 VRVN 1. S, VVRIVIN, 0... 003 | _s __ _ __ e I ì.. ~ ~ I position plus eight. SVVRVNTTNC ilO. 0301 Irl 11 MTVGFNSDI irxl iCTWn>i. l rFl VRVNTTNCH7 ; Subsequence score NTTNCHKC 10. 0201 19 MTVGFNSDIS 1 : 0. 005 21 HKCLLSGTY 6 j NSDiSSWR j 0. 020 ! j 17 TTNChKCLLS) 0. 004 18 jpTNCHKCLLS"1 0. 000 1 : 0 : 7- Fo-p o,, PISQVYR FO. 020 17 TTNCHKCLLS 004 TNCHKCLLS 0. 000 rT6r''''TTNCHKCL ! 0. 015 3'VGFNsDiSSV i M02 10 ! SSVVRVNTT 1 0. 000 11'I SVVRVNTTN il 0. 005 11 11 9 11 ISSVvRVNTTt10. 002 ! 1 ILg I ISSVVRVNT IL°°°° ! l SVVRVNTTN ISSVVRVNT 9 ISSVVRVNT SVRVTT] [EOQ27-F2 : 00f--7ii , z, == : 0 < Table XVI-109P1 D4v. 6 Table XVII-109P1 D4v. 6 Table XV-109P1 D4v. 6 N'terminal-A24-9-mers N'terminal-A24-10-mers , N terminal-A1101-10-mers Each peptide is a portion of Each peptide is a portion of SEQ Each peptide is a portion of SEQ ID SEQ ID NO : 13 ; each start ! D NO : 13 ; each start position is NO : 13 ; each start position is position is specified, the length specified, the length of peptide is. P P P 9, P 9 P P specified, the length of peptide is 10 I of peptide is 9 amino acids, and 10 amino acids, and the end amino acids, and the end position for ! the end position for each position for each peptide is the each peptide is the start position plus peptide is the start position plus j start position plus nine. ! nine. eight. Pos IF- _. ubsequce ! I'.. _.' IF VRVNTTNCHK 0. 030 0. 750 -- tl 22 z KCLLsGTYIF ll 0. 018'. t 10 ItSSWRVNTTi 0. 180 g T<H I _. _. _, m s-=-=weu L ~ KCLIS T 1° QO ! 1___. _.... ! _ _ _ . _... _ 21 HKCLISGTYI i 0100 ; CLLSGTYIFA [14SDISVV i [0 1-68 ; I ww..... .. _. __. ,. : 16 NTTNcHKCLL ; 0 010 j8 DISSVVRVN 0. 140, 6 ! NSDIsSWRV 0. 100 : FNSDISSWR. 008 ISSVVRV 14 RVNTTNCH C , O K K 6_'I, 5-jFy-Tic : H--ci 7 IF SDISSVVRVN 0 0211 _ _ _,, _, X s {r [2 TVGFnSDISS 0. 004 98 TNCHK S 0. 100 ~t __ Le__ w_ =^"ìl K IL . . __.... : I... W. ..... : , 11 SVVRvNTTNC 0. 003 3 VGFNSDISS. ; ^0, 100 ! 12 WRVnTTNCH 0 012 : W [w iw, @t WRvnTTñcH AW 17 vLTTNChKCLLS LO002 | 1 12 llWRVNTTNCll 0. 100 [1 Ir-E ; <rO01Oi 1 MTVGfNSDISm 3 0. 002 = '14 ; RVNTTNCHK 0. 030 II 3 oI VGFNsDISSV t1 o. ooo I 1L7 ilSDISSVVRVII 0. 015 Jl er<+ w ZFEHEj1 w ''' N'terminal-B7-9-mers IF- : E--LVVRvNTTNC 0. 003 NC _,...' 1." 0 # ^+ a, __s ì-speclle, e g p p lì VNTTNCHKCL 0. 09-0-1 11L9F--LS specified, the length of peptide is t.. lU ! SGTY [j [o, iUl ! ! CHJ., 0. 002j j 9 amino acids, and the end t position for each peptide is the ,. f 1 ii start position plus eight 21 ENCHK (L Table XVI 1-1 09Pl D4v. 6 N'terminal-A24-1 0-mers Subs Score 1 SSWrVNTTN ; 0, 000 £---------- ! 9 ISSVvRVNT 0. 000 Each peptide is a portion of SEQ ; T2..,..,. wRVNTTNC, 5 000 Li ID NO : 13 ; each start position is il t 16 ! NTTNCHKCiTl4000t ISVVR N...... I 17"., # TTNCHKCLL 4 000, 10 amino acids, and the end [--T : ED t ' ! start position ptus nine. ==-. CLLSGTY ! t0400 , start position plus nine, 22 KCLLSGTYI 0 400 I N'terminal-A24-9-mers | 1 5ì) t f I Each peptide is a portion of ; ps., "Subsequen Score : . ^rt, 5SDISSVV 0, 200., II Each peptide is a portion of 1l IL",-. 1 ll d. ll__ __ IL. _ lí SEQ ID N0 : 13 ; each starf 22 KCl. LsGTYIF 6 000 : g i ISSWRVNT 0 SEQ ID NO : 13 ; each star position is specified, the length : 16 NTTNcNKCL 3 4 000 of peptide is 9 amino acids, and l lo W jw of peptide is 9 amino acids, and the end osition for each ..- F-1- 7, 1 \NTTNCHKCL [4. 000 RQNTN I_. _. , :. .. 15 VNTTNCH14C 0100 2 TVG NSDIS 0. 1001 eight. 07 l9. IlSubsequencell Score F--17IjLNT-CK 0, 050 ! 17, ßTTNCHKCLLIt 6. 000 il 11 1 16 FNTTNC 4, 000 8 DIS 6 v {NTTNCHKCL} 4000 01 ; <r MTVGSiSD ! S g r C ISSV 2W1 18 ., TNCHKCLLS 002 =-------,---. LjLI2JM50) 18 TNCHKCLLS 0 jjEtCLLS_Y] Fit 3, 000 11 ErSVVRvNTTNC íGHOil llXw [2 ! LCLLSGi-Y-F-o c o-7 23 CLLSGTYIFA 7 RV 0. 02011 1Hl ! v59T 1 f ; Ir---7/S+VRV 1ioo2051 Table XVIII-109P Table XIX-109P1 D4v. 6 Each peptide is a portion of SEQ ; N'terminal-B7-9-mers 1 N'terminai-B7-10-mers l ìD NO : 13 each start position is) X l Each pepfide is a portion of SEQ Each pepfide is a portion of SEQ j 10 amino acids, and the end ID NO : 13 ; each start position is ID NO : 13 ; each start position is positon for each peptide is thé specified, the length of peptide is the 9 amino acids, and the end 10 amino acids, and the end,. st posit n plus nine. position for each peptide is the position for each peptide is the Pos H start position plus eight. start position plus nine. 2- !, 2. ooo : ! 22, 4fCLLGTYIF 2. 000 ; Jl Pos TL Subsequence 31Scorel I Pos ìl Subsequence ilScore +l NTTN HKCLL ffi u on c _. _ ___ c f __ C V . 23 CLLSGTYIF, O°00 ; . 1, VIVNtTNCHE<'0 001 : 15 Y VNTTnCHKGL f . 000 : rm _ _*., i 3. 1 _NSDISS 0 020 w oo t + F20 CHK 0. 010 Table XX-1 09PI 0 ; ! N terminal-83501-9-mers !, 1, 9 F NCHKGLLSG 0. 010 --- i 10 SSWrVNTTN'0. 500 ; - Each peptide is a portion of SEQ ID NO : 13 ; each start position is IF-NS Fp y 21 HKCLLSGTY 0. 002 , specified, the length of peptide is 9i-ìl 3. hi VGFNsDISSV | jEool I amino acids, and the end position for each peptide is the start ......... position plus eight. 0. 10 N terminal B7-10-mers , --. =- 16 NTTNCHKCL ; 1. 00 ; DISSvVRVN'f'0. 100 : epfide is a portion of SEQ Each NO : 13 ; each start position is ! 1-7 :] I-ATVGfNSDIS 0. 1000 iD NO : 13 ; each start position is 11 Oi EL<, WFãXFõ 10 amino acids, and the end ti poslbon for each pepEde is the il i-- start position plus nine. ,.. ISSWRVNT 0 500 : 11, SVVRvNTTNC 0. 100 ; position for each peptide is th ....... .. _. ; __ .... . _M it Subsequence'H, 1 l<, l SSWRVNTT,, jrõi ii 21 HiidiS, Eo 1 Subsequence g : c : o : re7 VNTT 0. 500 HKCLISGTY17 0. 0401 ! Dtr' ! S r" [ssw ! E7E"ss {o , 15 VNTTnCHKCL : 4 000 _. FNSDISS 0 400 S 4 GFNSdISSW 0. 020' 11, SVVRvNTTNC= 0500' ; 12 v VVRVNTTNC 0. 300' 5 FNSDiSSWR 0. 020 : -14 RVNTtNCHKC 0500 : ,. 21 HKCLLSGTY- 0. 200' 18 TNCHkCLLSG -0. 010' -, J _. _ _ í ;. _w = '15 VNTTNCHKCL F77, f EGTD I S- ; î I _ 9 ~ ; _t __ =.. ##">__. _. _... _. ~_. = ? _ í CHKC 0. 500 CLSGTY C. 2EO TNCHKCLLSG 0. 010i : ; ; ; =l i ; = s ; ;. 19. :",. NCHKcLLSGT"" OT100s , u15a., VNTTNCHK 0. 100 ; Table VIII-109P1D4v. 7 1X3t NCHKcLLSGT ilO. 100i31 3j 15 il VNTTNCHKC 33W 3 ; t Table V ; 11-109P1D4v. 7 1t VGFNSDISSV DISSV DEL oj i8 tr'ssvw [aioo (inrcHKjo : Each peptide is a portion of SEQ' NTTNCHKC_, Ilo. iooi N'terminal-Al-9-mers ; ID N0 : 15 ; each sSart position is i SS Oea ID NO : 15 ; each start position is , NSDIsSWRV^ v 0. 060" 4 '',, Y GFNSDISSV 0 030 amino acids, and the end position ; 21 HKCLISGTYI 0 040 7, SDISSWRV 0 020' for each peptide is the sfart . I.. ...... . ...... 1.,... _. posihon plus eight. for each peptide is the start i I...... : Pos, ^, Subsequence. ScoreM Fo-position plus eight. GFNSDISSV 10 9-20i F-j4- v RVNTTNCHK 0. 0201 }, TTNCK} I m 17, , TTNChKCLLS 0. 020 j 3 RVGFLUSS 0 050 i , Table XXI 109P1 D4v. 6 I Iu-- V. 075 ; N termnal B3501 10-mers , FNSDiSSVVR 0. 010 ;,.-, Table XXI-1 09PI D4v. 6 N'terminal-B3501-1 0-mers 7 SDISVVRVN ilO. 0 PLLLVSVVR 0. 020 EL29O"IL,,.",,, C, wH*, KCILSGTY~#. O0g 'e's a rfio of E Table Vtii-109P1D4v. 7 Tabte iX-109P1D4v. 7 Each pept ! de is a portion of SEQ N'terminal-A1-9-mers N'terminal-Al-10-mers 1 ID NO : 15 ; each start position is - specified, the length of peptide is : Each peptide is a portion of SEQ Each peptide is a portion of SEQ ID NO : 15 ; each start position is NO : 15 ; each start position is specified, the length of peptide is 9 specified, the length of peptide is 10 start osition IUS nine amino acids, and the end position amino acids, and the end position for ------- ---.' for each peptide is the start each peptide is the start position plus W19H3 . positiUn plus ei9ht. ¢ _. í} nine. S 1 i\C|< IF Pos I Subsequence LtrK} Pûs I Subsequence |I Scûrt^ E [<1R _ _ J _ _ì __~_ >L 20, LVSVVRVNT 0. 020., ; ; VGFLiISSSS". 0 003 17 PLLLvSVVRV 3. 022', m SSSSSLSPL. __ X 2. _FRVGLIISS. H » ___ l., _ 11 _,. 1 19 ssss LLVSVVRVN GFLIIS-oo §§sPLv ! w.. ...... ri. _.. ... .. .... .... _ I. __ 20 LVSVvRVNTT'2, 550 _ ; jf 8 tt IISSSSSLS jLO. 010 1 i MFRVgFLIIS tt 0. 000v [15 iI LSPLiLVSVV ii 0. 728 EEELitSSSO... . .."TT'SSSsSLSPL !'0 : 545' -6 FLIISSSSS 0. 010 T^ OF Table TableX-109P1D4v. 7. 1 0 I SSSSiSPLLL I 0i3s -F-Tl I _.. _.. _ _ : N'terminal-A0201-9-mers ssss F0. 007 4 VGFLIISSS m0. 003 Each peptide is aportion of SEQ ; ---w-w ID NO : 15 ; each start position is ; ; 18, F LLLVsVVRVN (0. 088' .,,,,-. FRVGFLIIS Fooo3 specified, the length of peptide is 9 amino acids, and tfe end posifion amino acids, and the end position -----, : for each peptide is the start t 5 i GFLIISSSS t1 0. 001 j positionpluseìght. 1 z õ 1 XLIAFa [GFL ° j uI Pos_ ! | Subsequence i| Score. 1 1< w R , 1. .. MFRVGFLII 0. 000"Pos Subseq uence Score 4 VGFLiISSSS 0. 003 ; EWl Cwi w1 XXwñv O. +i Table IX-109P1D4v. 7 "I N'terminal-A1-10-mers f _.. -IISSSSSL 4 993 ; 21 VSVVrVNTTN 0. 001 - [, Tosj [., §ubsequence Score N'terminal-Al-10-mers Each peptide is a portion of SEQ ID L G,--, NO : 15 ; each start position is Logg ) specified, the length of peptide is 10, 16 y SPLLLVSVV 1. 584 :'2 FRVGfLIISS 0. 000 : 'amino acids, and the end position for t ' FRVGfLIlss. 000 nine., 1'ilS 3_I each peptide is the start position plus'_, _MF\ l§ nine. r 6 FLIISSSSS 0-. 3-43 ! l I Aq n 11 f Pos Subse uence Score 10 SSSSSLSPL ! 0 329, ! Table XII-109P1 D4v. 7 j nce l Score Table XI 1-1 09Pl D4v. 7 Each peptide is a portion of SEQ F-1 g7-i F-. SSSLSPLLLV'Fo.-075-1 0. f39 F im-ID NO : 15 ; each start position is SSSLSPLLL for each peptide is the start 16 SPLLIVSVVR 0 050 19 l LLVSWRVN 0 024 position plus eight. specified, the length of peptide is 91 t| 19 II LLVSVVRVNT il 0. 020 i ii 3 fl RVGFLIISS f| 0015 j] 17 Uli PLLLVSVVR l0900i] 19 LLVSvVRVNT ; 0 020 3 RVGFLIISS 0. 015 : ; 15 LSPLILVSVV 0 015, 4 VGFLIISSS T 0 007' ; I il'l. ; _ 18 _LLLVSVVRV T 0. 900 ; il 6, I FLIIsSSSSL _1 0. 010 1 11 5 il GFLIISSSS'I °°°° <laiFloHõx il<i LLVSWRVN * . FLIIsSSSSL 0. 010 ;' (5 GFLIfSSSS '0 000 ; g FLIISSSSS W 0 060 ; _ ,., I ., .. for each peptide is the start 20 LVSVvRVNTT 0. 010 ; ; 9 ISSSSSLSP, O 000 : 1g. LLVSVVRVN 0. 013A ; ,, RVGFIIISSS 0, 010, RVGFLIISS 0. 012 ; 7 LIISsSSSLS. 0, 010 Table XI-109P1 D4v. 7 v '--.. . : I _.,.. C, ; 16 SPLLLVSW 0 009 il--la r'I 11 N'terminal-A0201-10-mers ! 1 i ~- . -- , IISSsSSLSP 0. 005 ; 13 SSLSPLLLV 007 Table XII-109P1 D4v. 7 Table XIII-109P1 D4v. 7 Each peptide is a portion of SET terminal-A3-10-mers ID NO : 15 ; each start position is Each peptide is a portion of SEQ Each peptide is a portion of SEQ ID 10 amino acids, and the end ID NO : 15 ; eachstartpositionis ! N0 : 15 ; each start position is specific, the length of peptide is 9 specified, the length of peptide is 10 ; amino acids, and the end position amino acids, and the end position for...... for each peptide is thé stars each peptide is the start position pius ULt).-9"J L§ ! L P P P P P P . _.. « : l w_... .. position plus eight. nine. .... "_.. _ _ _. : Dssj [o ! En rMLo'oooj 'rGF)) isssro' _ 12 SSSLSPLLL 0. 006 2 wFRVGiLIISS _ 0 000,,, / (FIISS 0. 006 ; 10 SSSSSLSPL 0. 005 Yy21 VSWrVNTTN ? f0. 000 ! 4 I SLSPILLVSV 0 004".. : , 8 I, ISSSSSLS 0. 004 ; u, GFLIiSSSSS 0 000"i--0 LVSVvRVNT 0.-00-2--v 14 SLSPILLV, SV 5iF7LI SSSSS rO. 001 SSSSLSPLL I'll. 7 Fo-7oo73 Table XIV-1 09PI D4v. 7 21 VSVVRVNTT 0. 002 t terminal-A1109-9-mers'-------------------------- 21 ! LYL\KIIVNTT ! [-- Each peptide is a portion of SEQ IN Nô : 15 ; each start position is LlISsSSSLS o. ooi specific, the length of peptide is 9 9 ! LLVSvVRVNT 0001 on i L ig-s-oi amino acids, and the end posifi for each peptide is the start . _.... .. . __i. .... . LIISSSS. 0 070 position plus eight. FRVGFLIIS 0. 000 p o------- T 9 ISSSSSLSP 0 000 Pos mSubsequence S'1. 2 ; SSSLsPLLLV 0, 000 : PLLLV 121 L PLL 1Each peptide is a portion of SEQ ID 1=8 L-LLYsvR-v ISSSSSLSPL-o. ooo i N termnal-A3-10 mers i ^ ! ----- LLsvyR) N oo NO : 15 ; each start position in suss specified, the length of peptide is 10 L 7-,, Fq. E-i-L-1Fi= amino acids, and the end position for) 04 _. SLS each peptide is the start position ! nme t = 20 LVSVVRVNT'0 002.'4 VGFLiISSSS 0 000 ; .. _... . ... _..... _.. _... a 1 __. _. . E M I Pos j Subsequence : Score w GFLIISSSS , 0 001 21 g VSVVrVNTTN 0. 000 i _§cor-jF I, w14 SLSPILLVSV.'0 450,' ;,, 93,,'". SSLSPLLLV 0. 001'Table XVI-109P1 D4v. 7 i ---- N'terminal-A24-9-mers "iriYLvVRVNT r6"1"SSSSS'I... J'24rs--) 'po -111,.. ID NO : 15 ; each start position is ", 17 PLLLvSVVRV I 0 090.". ; ;, 9. 2,.. r.. SSSLSPLLL,.",. 0. 000 ; specified, the length of peptide is 9 "'"2 (T)"LVSVvRVNTT'roTi)") rSSSSLSPL Ho. OOol amino acids, and the end position for each peptide is the start 18 LLLVsVVRVN 0 093 11 SSSSLSPLL j0, 00p position plus eight. d.. _. _.. I......... ...... l... _...... ....... : RVGFIIISSS __s. 0", 009 T. 15, _. T _LSPLLLVSV 0 000 : P b , os Su sequence W Score, position plus eight. issu U. ... (.. _. 1 iMFRVGFLII, 6000 ; 12- SSLsPLLLV 0. 005 ' 9 ISSSSSLSPs0. 000 1, . SSSSLSPLLT'4. 800 SSSsSLSPL : 0005 ; I _4., VGFLIISSS 000' 12 ; SSSLSPLLL 4000 i E .-ag--i _LSPLLLVSV ! 0. 000 : F Score 12-i SSSLSP-LLLV 1-'-6. o-6-5-' 9-F-1-ssss-Lsp-r6o-ool J 'S LSPLILVSVV : 0. 003 ' TableXV-109P1D4v. 7' _. .. RVGF 0. 240 ; !---N terminal A1101-10-mers SPLILVSVV Table XV-1 09PI D4v, 7 I. . . .. .. . i ., a MFRVgFLIIS 0 000 _ MFRVGFLII : z w = == F = Table XVI-109P1 D4v. 7 Tabie XVII-109P1 D4v. 7. t Each peptide is a portion of SEQ l N'terminal-A24-9-mers N'terminal-A24-1 0-mers i. ID NO : 15 ; each start position is .... _ I Each peptide is a portion of SEQ Each peptide is a portion of SEQ} specl, leu,."e, eng."u, pep. lue ss ID NO : 15 ; each start position is ID NO : 15 ; each start position is position for each peptide is the 'g P p p'g p p siart position plus nine. amino acids, and the end position 10 amino acids, and the end for each peptide is the start position for each peptide is the j f Pos j Subsequence jjScore . = position plus eight. start position plus nine.. 9. <gO0 k.. _ Sõ ; i Snce k ; ; 1T E. _ rw [m~"2 r-<iw iX-sss<-L, E-q--s---I L s-u Ls q ye-n c e-,, L'Sub eqL.-,- £ 18 ; LLLVSV1/RV 0. 150 ; a 17 ; PLLLvSVVRV i 015 ; ; y---FLIIsSSSSL 4-0-00- : L §SSISPLLL 4. 0001 SVVRVNTT IF 18-0 v , w---.-- 12 SSSLsPLLLV, 0300 ; SSSSSLSPL F 18 1 [ :-tF-l [-PLLLvS-VVRV i 0. 0152 o : LLLVSWRyjL9j40j)--=-=--==----ri6 SPLUVSVVR 0. 200 =" 16 SPLLIVSVVR 0. 200. F13-1 SSLSPLLLV 0. 150 l ~ ID NO : 15 ; each startposition is'L 14. t| SLSpILLvsv jQ P 1_.. I.. _. __.. _. _..., _.. I_.. _ 8) fiSSSSSLS j 0. 100 j specified, the) ength of peptide is 9 ri9"rLLVSvVRVNT i ! 0150 L LLVSVVRVNY o. 150 f amino acids, and the end position I-------- (. _ . .. . _.. i position plus eight.'18 LLLVsVVRVN 0 020 .. 17,, PLLLVSVVR 1 0. 00 i-p--os Subse uence Score : (13 -SSLS LLLV 0-. 020 -FT] I-. RvF Ll § FEo 1 7- L P 11 G S2 E Subsequence < 1<> W7 [H°S ; <SSSX 'T. Table XVN-10SP1 D4v. 7... : _. _ , 19 SSSSLSPLL 4 000 : 21 VSVVrVNTTN 0020 ; N'terminal A24-10 mers . w--------.. . .- < C<lw l30-oõ lTorõ I m ---- 12 SSSLSPLLL., 4 00 7 ;. LIISsSSSLS 0. 020 : Each peptide is a portion of SEQ j 7 LIISSSSSL 4. 000 i m17 PLLLvSVVRV 0. 020 0 ID NO : 15 ; each start position is L [ISSSSSL. 000 1-i L-L-LLvq-y) Rv- Ko : 2, (specified, the iength of peptide is riol SSSSSLSPL'rOOO""") !'pR\FLiiS JJO. OM 10 amino acids, and the end -w ! 3 20" LVSVVRVNT : ; 0. 750 ; 8 IISSsSSLSP 0. 010 ; osition for each e tide is the PP I start position plus nine. I t<2HiFiiHFLH. start position plus nine. 1 MFRVGFLII FRVGfLilSS 0. 0021 XI Pos xL Subsequence I} Score it 13 jl SSLSPLLLV. l 0. 300 1 i GFLliSSSSS if O L6 jj FLllsSSSSL 16. 0 Ij'15 |LSPLLLVSV 4 , FLIIsSSSSL j 6. 000 15 a Y LSPLLLVSV ; 0. 200 j I L GFLIISSSSS Lliss-ss§L (--o 1=5 v- [-T---- --', Each peptide is a portion of SEQ 4. 80 if--iti 9 ISSSsSLSPL 4. 000 3 RVGFLIISS ; 0. 100 p N0 : 15 ; each start position is GFLIiSSSSS 0 750.. ". 9. 4, j SLSPLLLVS 0 020ej specified, the length of peptide is 9 ! r" rJFRiis 0500 ,,,) 0. 020' smino acids, and the end position 11 -- ; « 11 for each peptide is the start 11 for each peptide is the start i for each peptide is the start 1 '. 9 9. ^w., LLVSvVRVNT 0. 210 ° I 8 " IISSSSSLS : 0. 020 '' '' 'M i 1jl 19 iL LLV. SVVRVNT t8 ft 8 1l. ! ! SSSL-s l0. 020. i1w1 X 1 [E31 Pos Subsequence 11 Score N0. 210 S. 5, * f ir=~ 9rS ~---fi i... L= = 11 15, {LSPLILVSVV il0. 180,''} 5 tI GFLIISSSS 1 0. 00 2, t, O _" T 13T SSLSp 0. 180 : ; 32 jFRVGFLIIS 0. 002 i g SPLLLVSVV 4. 000 i "^, + i = __. ! t, I SSSSS SP _ 1 5. 000 Table XIX-1 09PI D4v. 7 VGFLilSSSS-, [0 1-40 ! o ii SSLSPLLLV'I. 000 !) 4) f"VGFLiiSSSS"10. 140 Tab) eXiX-109P1D4v. 7 ! t'iT""qf L 14 _i ! SLS_ILLVSV_10144l ff < 0 >ll ; t __ . i. _ _ _-. 4. 21 VS/VRVNTT 0. 500 ! irer SSSLsPLLLV {[X3, RVGFLIISS SPLLI 18_ [_LLLVSVVRV F T} 1 D4t7 _ Ta VA Table XX-109P1 D4v. 7 Table XXI-109P1 D4v. 7 j Table X-109P1 D4v. 8 v N'terminal-B3501-9-mers 1 l N'terminal-B3501-10-mers. A0201-9-mers termi : Each peptide is a portion of SEQ Each peptide ! s a portion of SEQ Each peptide is a portion of SEQ ID NO : 15 ; each start position is ID NO : 15 ; each start position is.. D NO : 17 ; each start position is specified, the length of peptide is 9 specified, the length of peptide is specified, the length of peptide is 9. amino acids, and the end position 10 amino acids, and the end amino acids, and the end position for each peptide is the start position for each peptide is the for each peptide is the start position plus eight. start position plus nine. position plus eight. ...., iHõE Subsequence I. e. os i ; g H |) Subsequence lScore l ~ S 9 _ _ _ w___.. . ___.. _. .. . =.. . __. ... . __. _ _... __ _... , . .. . . _. : E 1 8 Ii 3 » 1 14 SLSPLLLVS 0. 100 5 GFLIiSSSSS 0 010 : 4 PGLKKEITV 0. 037 ; w_. w _ : r : _ w. . tc :. cr_... 0 : LVSWRVNT 0. 100 I ; IPGLfCKEIT 0. 017 : 8 Table VIII-109PID4v. 8 oi=o KKE VQP 7 OC5 IL Each peptide is a portion of SEQ F- [___TFIPGLKKE o F ID NO : 17 ; each start position is-"--'--- ( L 4 iC<jLo 100 1 = < 3Wi specified, the length of peptide is 9 ; 6 LKKEITVQP 0. 000 t. . . . w _. . 5 GFLIISSSS 0. 010 j amino acids, and the end position ! __. _ t ... . ___. __ for each peptide is fhe starf s2 A FRVGFLIIS,. 0 010, ; position plus eight. Table XI-109P1 D4v. 8' A0201-10-mers 17 peptide is a portion of SEQI I _. _.. . i. __. _.. _.. .. t.. _.. Pos,.,. Subsequence.. ScoreF ! Each peptide is a portion of SEQ p"M"KKEITVQPT 0. 045 ; ; ID N0 : 17 ; each start position is Table XXI-109P1 D4v. 7 ; 2 FIPGLKKEI 0 010.''specified, the length of peptide is N'terminal-B3501-1 0-mers ..,.. _ ___. -' 10 amino acids, and the end I P (LKK li [EO O7 Each peptide is a portion of SEQ , D NO 15 each start position is 8 KEITVQPTV o. ooi start position plus nine. , 1., a pos, specified, the length of peptide is-.-Ol b eq c o r : e : 10 amino acids, and the end ;-F§ : : : ,, . PGLKKEITV 0 000, 5 . FIPGIKKEIT 0. 947 ! position for each peptide is the},'- start position plus nine. L 'v | v, 0. 0222 ISSSSSLSPL 5. 000 L7 5. O=LO SSSSsLSPLL mt oAl-lO-mers il ; , ; SSSSISPLLL 5. 000 5. 000 Al-10-mers STFIPGLKKE E.. _. ... 5_, _ LSPLILVSVV 1 000 T.,... GLKKeITVQP 0001 - -----ID N0 ; 17 ; each start posifion is : FLIIsSSSSL,., j 1,. 000 specified, the length of peptide i........ | 12 il SSSLsPLLLV, 0iioE 10 amino acids, and the end 2 PGLKkEITVQ 0. 000 position for each peptide is the ; 21", m"", , VSWrVNTTN, (0. 500, start position plus nine. "",",, v i. ___... £ Pos. Subseq Score ; -- : A3-9-mers il 16 ß} SPLLIVSVVR, 10. 200ß1 li 8 -.. Sp a : LKItLQTi [- 4 SLSPILLVSV 0. 200,', Each peptide is a portion of SEQ : Each peptide is a portion of SEQ 3 RVGFIIISSS 0. 200 specified, the length of peptide is 9 | +| LLLVsVVRVN irO91 amino acids, and the end position [ I __ _. I _ _. 2'TFIP LKKEI 0 005. I for each peptide is the start _99 ; LLVSvVRVNT 0. 100, 4 i ; STFIpGLKKE ;'0, 003j ; posifion plus eight.' wrmHl r9., < w1 Er< < , 4 VGFLiISSSS 0. 1. 00', 9 KEITvQPTVE 0 000, f5. GLKKEITVQ 0 090 CLIISsSSSLS 0 : 100 5 ; yPGLKkEITVQ 0000 2 FIPGLKKEI 0. 045 : MFRVgFLIIS ! 0. 030 6 t GLKKeITVQP 0 000 , 8 KEITVQPTV ; 0. 004 17 My PLLLvSVVRV ; 0. 020 ., IPGLKKEIT, 0. 001 ; [w3w1 Irxrr°°° =6', [GLKKelTVQP o. ooo 0. 004 [s > It A3-9-mers aUs »/109PI 8 I A24-10-mers Tabie XII 109P1 D4v. 8.. ... _... _. :. ... Table XVII-109P1 D4v. 8 A3T) ers Tab) eXV-109P1 D4v. 8 iA24-10-mers ? wiz k Each peptide is a portion of SEQ.. Each peptide is a portion of ID NO : 17 ; each start position is Each peptide is a portion of SEQ SEQ ID NO : 17 ; each start specified, the length of peptide is 9 ID NO : 17 ; each start position is position is specified, the length amino acids, and the end position specified, the length of peptide is of peptide is 10 amino acids, for each peptide is the start 10 amino acids, and the end and the end position for each position plus eight. position for each peptide is the peptide is the start position plus p ir s b = l starL position plus nine. _ l nine. I_ q _. _. _. . KKEITVQPT'0. 001 "_Ps Subsequence Score ( Pos,.. Subsequence'Score. [S : c :] DEI'PGLKKEiTVJ TOM ; !"-. J. EGLkKEiTVj IZIjLjPGLkKEiTVjLp. 100 8 KKEItVQPTV 0. 042 , = _ _. _.. g _ _............ l=i l 6 1 GLKKelTVQP 0. 001 j I 7 LKKEiTVQPT 0 0. 014 F 11 ( KKE _P ! SelTVQP OO 1L - (FL 7= TQ |<111-109PlD4v. 8 i i 8 [t KKEltVQPTV jjjO. 001 ! | STFlF1FS011 A3-10-mers i i ; vlHii Xlo A3-1 0-mers FIPGIKKEIT 0, 000 [EiTy in irv wr = __ Each peptide is a portion of SEQ ; g , T KEITvQPTVE ; 0. 000 ? , 5 PGLKkEIT Q 0. 002 ; ID NO : 17 ; each start position is specified, the length of peptide is t =. _ll=. w_ 10 amino acids, and the end 5 JPGLKkEiTVQj (jMOO Table XViii-109P1D4v. 8 __ _ : L g7_g_mers position for each peptide is the.. BT--mers i-start position plus nine. Each peptide is a portion of SEQ ---- s TableXVI-109P1 D4v. 8 Pos ; Subsequence Score : ID N0 : 17 ; each start position is 1 : -T-al- lv _r I | jl specified, the length of peptide is IL6< aL =GLKKelTVQp 11 0 090 1 1} Each peptide is a portion of SEQ 9 amino acids, and the end i tl5Ei 01 ID NO : 17 ; each start position is specified, the length of peptide is start position plus eight _, IPGLkKEITV ;. 0004 ; 9 amino acids, and the end iti+ {i-O « position for each peptide is'the start position plus eight. 3 3 IPGLKKEIT 2 000 KKEItVQPTV 0. 001, l j...... r .. i....... Pos Subse uence Score ; 2 FIPGLKKEI 0 400 ^ ' TFIPgLKKEI 0, 001 : I_. _. . _ I... q... ..... _. _ (_. _.... . _ _. . _ I 7 ; LKKEiTVQPT C0. 000 ; _f _ I. PGLKKEI ; 1 980i ; 8 KEITVQPTV 0. 020 2 ! l 11. 9801 = ! 9 J) lKEiQPTyEjLo L-LKKEJTjalOO L. JGLKKEiT [o : 020J ! r PGLKkEiTVQ' [000 LJ J'FiPGLKKEj [o [5 [KErrVQ] j) 10 L ji, Vw v $1 u-vuu U mT0i Ti< [ W T< <Hl TY < TI Al 101-9-mers EITV LI _ each peptide is a portion of SEQ 5 GLKKEITV'0. 010 il NO : 17 ; each start position is specified, the length of peptide is 9, B7-1 0-mers B7-10 mers ! amino acids, and the end position for each peptide is the star Each peptide is a portion of SEQ A24-1 0-mers ID NO : 17 ; each start position is specified, the length of peptide is Each peptide is a portion of 10 amino acids, and the end T 8 [X< 0. Wi SEQ ID NO : 17 ; each start j position for each peptide is the ~ position is specified, the length g start position plus nine. It 2 FIPGLKKEI 0. 002E p p ptg E start position plus nine jf _.. I ..... e of peptide is 10 amino acids, -==-- Oil} and the end position for each | eI Pos 1I Subsequence IScore. m peptide is the start position for each '1 TFIPGLKKE ; 0. 000 ! nine. (3y FIPGI-4CKEIT 0. 100i --- Pos ! Subsequence Score 2 TFIP LKKEI 0. 040v 4 PGLKKEiTV ! 0. 000j =L--. . JDPgLKKEi 0 TFIPgLKKEI , 11880 7 LKKEiTVQPT 0 010 7 KKEITVQPT i K V. Q.. P. T LO. l , 0. 000 . _,. __. 6 LKKEITVQP 0. 000-.. . _ . I . x ! = ==E ==== Table XIX-109P1 D4v. 8 Each peptide is a portion of SEQ (Each peptide is a portion of SEQ t B7-10-mers iD NO : 17 ; each start position is)) D NO : 17 ; each start position is specified, the length of peptide is l specified, the length of peptide is Erh Pan s pr cn aF SEQ spesmed, the tength of peptide is t speciñed, the length of peptide is Each peptide is a portion of SEQ g amino acids, and the end f i 10 amino acids, and the end spedor posmonforeachpepMeisthe posionforeachpeptideisthe ID amino acids, and the end l star position piu5 eight. star position p s nine. ! position for each peptide is the} Pos i > ; Scor } start position pius nine. 1 ii 3 HiiiiCi2 000 ;. =-=. =-> e v. __ _ ____, _ =,. _, li_ _. ll, __ _.,. ìl e. __ Subsequence g3 lt hPGLKKéI} 1t _< _I GLkKEITV ! 4. 000 wo ~ ^o ! l * GLK961T\'QP [3 _ 5 >. 0hO45 i O5tO < v LX KKEIVQPTV _t 9 [0S0 l t_ 7. J LKKEiTVQPT 0. 06 ; PGLKIeEITVQ" : 0 001 ; LKI (EITVQP 0 006 E ; _ _ KeITVQP 0. 030 ; I 6 I LKKEITVQP \ \ [ 7 | KKëITVQPT l 0 006 il 8 g| KKEitVQPTV {t0a012 IPGLKKEITV 4. 0001 ! Tabte XX-109P1D4v. 8'"T'tt TFtPGLKKE) foo01 Ijlj'010 ..... l ltFiitõ 00i t'SteXX)-109P ? M8) Q Table XXI-109P1 D4V. 8 I ? 1 H I. ... _ B3501-1 O-mers * = _== Tables XXII-XLIX : Table XXII-109P1 D4v. 1 Table XXIi-109P1 D4v, 1 Table XXII-109P1 D4v. 1 A1-9-mers A1-9-mers A1-9-mers Each peptide is a Each peptide is a Each peptide is a portion of SEQ ID NO : portion of SEQ ID NO : portion of SEQ ID NO : 3 ; each start position is 3 ; each start position is 3 each start position is specified, the length of specified, the length of specified, the length of peptide is 9 amino peptide is 9 amino peptide is 9 amino acids, and the end acids, and the end acids, and the end position for each position for each position for each peptide is the start peptide is the start peptide is the start position plus eight. position plus eight. position plus eight. l l l ll N LEEQTMGKY|2 231 HTRPVG QV I02 | REETPNHKL |i 59 TAMQFKLVY 22 34 MPENVLIGD 96 319 ETPNHKLLV 14 570 FT_HNEYNFY 22 78 EEDTGEIFT 16 411 VFSNQFLLE 14 807 T_SDYVKiLV 22 90 RIDREKLCA 16 514 SLDCRTGML 14 20 HSGAQEKNY 21 109 EVEVAILPD 16 542 AKDNGVPPL 14 418 LETAAYLDY 21 132 INDNAPLFP 16 572 HNEYNFYVP 14 495 SGPNAKINY 21 163 AVDPDV_G1N 16 612 ENDDFTIDS 14 594 VTDPDYG_DN 21 401 DHEIPFRLR 16 644 KA_EDGGRVS 14 985 SSDPYSVSD 21 531 E_KEDKYLFT 16 668 DNKPVFIVP 14 364 VNDTWLSE 20 631 FDREKQESY 16 681 SYELVLPST 14 370 LSENIPL_NT 20 738 KCDVTDLGL 16 720 TRDLFAIDQ 14 674 IVPPSNCSY 20 797 NT_EIADVSS 16 758 QPDSLFSW 14 789 ST_EAPV_TPN 20 802 DVSSPT_SDY 16 779 ATLINELVR 14 168 VG_INGVCNY 19 897 DSDGNRVTL 16 851 NSEWATPNP 14 F5974 NVPSIDI_RY 19 69 TG_DVPLIRI 15 904 TLDLPIDLE 14 741 VTDLGLH_RV 19 100 IPRDEHCFY 15 967 PLDNTFVAC 14 931 DSPDLARHY 19 115 LPDEIFRLV 15 91 C_SSSSSDPY 19 207 LDREEKDTY 15 Table XXIII 109P1D4v. 1 116 PDEIFRLVK 18 415 QFLLETAAY 15 A0201-9-mers ru ENSAINS_KY 18 423 YLDYESTKE 15 Each peptide is a portion ouf SEQ ID NO : 3 ; each 329 ASDGGLMPA 18 424 LDYESTKEY 15 start position is 45 specified, the length of 991 VSDCGYPVT 18 591 LITVTDPDY 15 peptide is 9 amino acids, 0 ans the end position for each peptide is the start position plus eight. 251 ETEIEVS_IP 17 688 STNPGTVVF 15 273 ATDADIGEN 17 705 T_GMNAEVRY 15 114 fLPDEIFRL 27 354 SIDIRY (VN 17 988 PYSVSDC_GY 15 416 FLLETAAYL 27 385 VTDKDADHN 17 6 KTGDVPLIR 94 43 LLKDLNLSL 26 399 FTDHEIPFR 17 148 IPENSAINS 14 333 GLMPARAMV 26 528 LDREKEDKY 17 219 EI4DTYVMKV 14 520 GMLTVVKKL 26 ELSPVFTHNEY|E | IGENAK ! HF | 31 LIGDLLKDL |i 727 DgETGNITL 17 311 IKEPLD_REE 14 294 NIARRLFHL 24 | KPDSPDLAR |g | SLDCR_GML i Table XXNI 1 || jTableXXIII 109P1D4v. 1 | |TableXXIII 109P1D4v. 1 | A0201-9-mers A0201-9-mers A0201-9-mers Each peptide is a portion Each peptide is a portion Each peptide is a portion of SEQ ID NO : 3 ; each of SEQ ID NO : 3 ; each of SEQ ID NO : 3 ; each start position is start position is start position is specified, the length of specified, the length of specified, the length of peptide is 9 amino acids, peptide is 9 amino acids, peptide is 9 amino acids, and the end position for and the end position for and the end position for each peptide is the start each peptide is the start each peptide is the start position plus eight. position plus eight. position plus eight. 17 AVAGTITVV 24 546 GVPPLTSNV 20 369 VLSENIPLN 18 31 NLLLNEVTI | 31 LTSNV_VFV | | ALITV_DKD | F64-1 KLVYKTGDV 23 656 SAKVTINV ! 20 403 EIPFRLRPV 18 231 STA1LQ_VSV 23 65 KVl'INWDV 20 480 SPGIQLTKV 18 307 GLITIKEPL 23 715 fVGGNTRDL 20 496 GPNAKlNYL 18 3I PLNTKIALI 23 725 AIDQETGNI 20 601 ILDENDDFT 18 539 TILAKDNGV 23 777 TNATLINEL 20 617 TIDSQTGVI 18 745 GLHRVLVKA 23 781 LINELVRKS 20 693 TWFQVIAV 18 810 YVKILVAAV 23 826 VV1FITAVV 20 733 ITLMEKCDV 18 813 ILVAAVAGT 23 GTYlFAVLL 19 734 TLMEKCDVT 18 X| VLIGDLLKD 22 12 VLLACVVFN 19 748 RVLVKANDL 18 '74T1) VTDLGLHRV 22 22 GAQEKN_YTI 19 757 GQPDSLFSV IEX 816 AAVAGTITV 22 135 NAPLFPATV 19 762 LFSVVIVNL 18 9 IFAVLLACV 21 162 AAVDPDVGI 19 780 TLiNELVRK 18 X RIEEDTGEI 21 303 NATTGLITI 19 814 LVAAVA_GTI 18 124 KIRFLIEDI 21 326 LVLASDGGL 19 822 ITVVVVIFI 18 fol SAINSKYTL 21 377 NTKIALITV 19 955 PLNSKHHII 18 301 HLNATTGLI 21 438 AADAGKPPL 19 958 SKHHIIQEL 18 356 DIRYIVNPV 21 503 YLLGPDAPP 9 990 SVSDCGYPV 18 360 IVNPVN_DTV 21 542 AKDNGVPPL 19 YIFAVLLAC 17 536 YLFTILAKD 21 583 LPRHGTVGL 19 57 LTTAM (FKL 17 743 DLGLHRVLV |E E31 FTIDSQTGV IEI EI GARIDBEKL IE 820 GTITVVVVi 21 818 VAGTITVVV 19 143 VINISIPEN 17 825 VVVIFITAV 21 881 LLLNFV_TIE 19 156 SKYTLP_AAV 17 999 TTFEVPVSV 21 903 VTLDLPIDL l9 65 DPDVGINGV 17 50 SLIPNKSLT 20 914 QTMGKY_NWV 19 179 IKSQNIFGL 17 127 FLIEDIfVDN 20 LLSGTYIFA 18 256 VSIPENAPV 17 234 ILQVSVTDT 20 LSGTYIFAV 18 320 TPNHKLLVL 17 270 QLNATDADI 20 13 LLACVVFHS 18 327 VLASDGGLM 17 298 RLFHLNATT 20 51 LIPNKSLTT 1$ 36 WLSENIPL 17 334 LMPARAMVL 20 95 KLCAGiPRD 18 379 K1AL1TVTD 17 337 ARAMVLVNV 20 120 FRLVKIRFL 18 482 GIQLTKVSA 17 340 MVLVNV_TDV 20 21 hLVKIRFLI 18 493 ADSGPNAKI 17 347 DVNDNV_PSI 20 213 DTYVMKVKV 18 586 HGTVGLITV 17 359 YlVNP_VNDT 20 276 ADIGENAKI 18 685 VLPSTNPGT 17 428 STKEYA_IKL 20 283 KIHFSFSNL 18 761 SLFSVVIVN 17 TableXXIII 109P1D4v. 1 Table XXIII 109P1 D4v. 1 |'jTableXXIII 109P1D4v. 1 A0201-9-mers A0201-9-mers A0201-9-mers Each peptide is a portion Each peptide is a portion Each peptide is a portion of SEQ ID NO : 3 ; each of SEQ ID NO : 3 ; each of SEQ ID NO : 3 ; each start position is start position is start position is specified, the length of specified, the length of specified, the length of peptide is 9 amino acids, peptide is 9 amino acids, peptide is 9 amino acids, and the end position for and the end position for and the end position for each peptide is the start each peptide is the start each peptide is the start position plus eight. position plus eight. position plus eight. 764 VVIVNLF 6 FHIIQELPLD ln5 '795 TPNTEIADV 1 934 DLPRHYKSA °I6 9i0 NTFVACDSV 15 89 AGTITVVVV 17 100 HTRPVG_lQV 16 983 SSSSDPYSV 15 965 ELPLDNTFV 17 41 GDLLKDLNL 15 995 GYPVTTFEV 15 1006 SVHTRPVGI 17 58 TTAMQFKLV 15 44 L. KDLNLSL ! 14 El DLLSGT_YIF 16 146 ISIPEN_SAI 15 46 Dl. NLSLIPN 14 10 FAVLLACVV 16 160 LPAAVD_PDV 15 66 VYKTGDVPL IE ! 42 DLLKDL_NLS 16 170 INGVQNYEL 15 106 CFYEVEVAI 14 49 LSLIPNKSL 16 181 SQNIFGLDV 15 111 EVAILPDEI 14 60 AMQFKLVYK 16 182 QN1FGLDVI 15 113 AILPDEIFR 14 67 YKTGDV_PLI 18 229 RSSTAILQV 15 115 LPDEIFRLV 14 83 EIFTTGARI 16 263 PVGTSV_TQL 15 128 lfEDINDNA 14 17 FYEVEV_AlL 16 284 iHFSFSNLV 15 137 PLFPATVlN 14 117 DEIFRLVKI 16 287 SFSNLVSNI 15 138 LFPATVINI 14 145 NISIPENSA 16 338 RAMVLVNVT 15 147 SIPENSAIN 14 197 KMPQLIVQK 16 374 IPLNTKIAL 15 159 TLPAAVDPD IE ! 233 AILQVS_VTD 16 396 VTCFTDHEI 15 183 NIFGLDVIE 14 290 NLVSNIARR 16 448 QSAMLFIKV 15 211 EKDTYVMKV 14 291 LVSNIARRL 16 450 AMLFIK_VKD 15 232 TAILQVSVT 14 300 FHLNATTGL 16 451 MLFIKVKDE 15 248 VFKETEIEV 14 432 YAIKLLAAD 16 504 LLGPDAPPE 15 250 KETEIEVSI 14 F2-1 AIKLLAADA 16 517 CRTGMLTVV 15 310'TfKEPLDRE 14 435 KLLAADAGK 16 590 GLITVT_DPD 15 324 KLLVLASDG 14 436 LLAADAGKP 16 624 VIRPNISFD 15 329 ASDGGLMPA 14 S| KEDKYLFTI IEG HIVKAEDGGRV|Eç XIMPARAMVLV|EX EI NVTVFV_SII 16 651 VSRSSSAKV 15 339 AMVLVNVTD 14 587 GTVGLITVT 16 688 STNPGTWF 15 344 NVTDVNDNV 14 599 YGDNSAVTL 16 703 NDTGMNAEV 15 362 NPVNDTVVL 14 602 NSAVT_LSIL 16 707 MNAEVRYSI 15 388 KDADHNGRV 14 655 SSAKV_TINV 16 742 TDLGLH_RVL 15 412 FSNQFLLET 14 667 NDNKPVFIV 16 767 IVNLFV_NES 15 465 VFTQSFVTV 4 722 DLFA (DQET 16 769 NLFVNESVT 15 483 IQLTKVSAM 14 754 NDLGQPDSL 16 75 KHSPKNLLL 15 500 VCINYLLGPD 14. 760 DSLFSVVIV 16 897 DSDGNRVTL 15 507 PDAPPEFSL 14 771 FVNESVTNA 16 904 TLDLPIDLE 15 516 DCRTGMLTV 14 E| PTSDYVKIL 16 906 DLPID_LEEQ 15 540 ILAKDNGVP 14 TaMeXXHh09PtD4v. 1 TaMeXXV-tTable XXV-t A0201-9-mers 11 09Pl D4v. 1-A3-9-mers-9-mers Each peptide is a portion Each peptide is a Each peptide is a of SEQ ID NO : 3 ; each portion of SEQ ID NO : portion of SEQ ID NO : start position is 3 ; each start position is 3 ; each start position is specified, the length of specified, the length of specified, the length of peptide is 9 amino acids, peptide is 9 amino peptide is 9 amino and the end position for acids, and the end acids, and the end each peptide is the start position for each position for each position plus eight. peptide is the start peptide is the start position plus eight. position plus eight. 552)) SNVTVFVSI 14 | THNEYNFYV IEi \ | TLINELRK | | tVNPVNDTV tri SNGSYELVL 4 27 KLDREfCEDK 26 74 RVLVKANDL 20 R| LPSTNEGTV |E m| GVQNYELIK |E E| WlFI_W |E MOl NPGTVVFQV 14 407 RLRPVFSNQ 24 17 WFHSGAQE 19 706 GMNAEVRYS 14 $ VIFfTAVVR 24 116 PDE_IFRLVK 19 714 SIVGGfVl'RD 14 $39 APNLICAAQK 24 189 VIETPEGD6C 19 768 VNLFVN_ESV 14 4 AYLDYESTK 23 218 KVKVEDGGF 19 773 NESVTNATL 14 674 IVP_PSNCSY 23 220 KVEDGGFPQ 19 784 ELVRKSTEA 14 841 HL_KAAQKNK 23 384 TVTDKDADH 19 812 KILVAA_VAG 14 972 FVACDSISK 23 416 FLLETAAYL 19 878 PKNLLLNFV 14 12 V. LACVVFN 22 433 AIKLLAADA 19 895 DVDSDGNRV 14 233 AILQVSVTD 22 479 NSPGIQLTK 19 948 FQIQPETPL 14 518 RTGMLTWK 22 535 KYLFTILAK 19 962 IIQELPLDN 14 623 GV (RPNISF 22 549 PLTSNVTVF 19 662 NVVDVNDNK 22 588 TVGLITVTD 19 TabIeXXIV 814 LVAAVAGTI 22 665 DVNDNKPVF 19 109P1D4v. 9 833 WRCRQAPH 22 802 DVSSPTSDY 19 A0203-9-910 DLEEQTMGK 22 864 MIMMKKKKK 19 mers 56 SLTTAMQFK 21 2 DLLSGTYIF 18 No Results 65 LV_YKTGDVP 21 38 VLIGDLLKD 18 Found. 167 DVG_1NGVQN 2 60 AMQ_FKLVYK 18 | RL_HLNATT | | RIDREKLCA IEB Table XXV-324 KLLVLASDG 21 212 KDTYVMKVK 18 I 109P1 D4v. 1-A3-9-mers 379 KIALITVTD 21 267 SVT_QLHATD 18 Each peptide is a 524 WKKLDREK 29 333 GLMPARAMV 18 portion of SEQ ID NO : 3 ; each start position is 582 NLPRHGTVG 21 445 PLNQSAMLF 18 specified, the length of 740 DVT_DLGLHR 21 487 KVSAMDADS 18 peptide is 9 amino 744 LGLHRVLV6C 21 540 ILAKDNGVP 18 acids, and the end position for each 812 KILVAAVAG 21 642 YVKAEDGGR 18 peptide is the start 817 AVAGTITVV 21 645 AEDGGRVSR 18 position plus eight. ggp NLLLNFVTI 21 658 KVTINWDV 18 921 WVT_TPTTFK 21 68 STNPGTVVF 98 650 RVSRSSSAK 31 435 KLLAADAGK 30 50 SLIPNKSLT 20 694 VVFQVIAVD 18 11 AVLLACWF 28 113 AILPDEIFR 20 697 QVIAVDNDT 98 m| NVLIGDLLK |E ==="''=r== 197 KMPQUVQKO r745 GLHRVLVKA 18 Table XXV-Table XXV- 109P1D4v. 1-A3-9-mers 109P1D4v. 1-A3-9-mers 802 DVSSPTSDY 30 Each peptide is a Each peptide is a 665 DVNDNKPVF 28 portion of SEQ ID NO : portion of SEQ ID NO : 3 ; each start position is 3 ; each start position is 241 Dl'NDNHPVF 26 specified, the length of specified, the length of l | ENVLIGDLL | peptide is 9 amino peptide is 9 amino l E31 EVEVAILPD | acids, and the end acids, and the end position for each position for each | DVNDNVPSI | peptide is the start peptide is the start 1002 EVPVSVHTR 25 position plus eight. position plus eight. fez DVIETPEGD | S|AV_RCRQAP|E E|SVTDTNDNH|E | NVPSIDIRY | USiDiRYj [31RCbQAPHLl XITNDNHPVFK\0@ g| PVFSNQFLL | 871 KKK_KKHSPK 18 277 DIGENAKIH 16 40 PVFSFLL 4 Fl-006] 9-Fl I F 102 EVPVSVHTR 18 293 SNIARRLFH 16 623 GVIRPNISF 24 F3411 ln6 1006 SVHTRPVGI 18 304 ATT_GLITIK 16 10 EVRYSIVGG 24 F95 F354] 23] 43 LLKDLNLSL 17 341 VLVNVTDVN 16 118 EIFRLVKIR 23 '5) LiPNKSLTT l7 tNyPSiDiRY ETEiEVSiP mLGLHR@ mp 95 KLCAGIPRD 17 354 SIDIRYIVN 16 263 PVGTSVTQL 23 122 LVKlRFLlE 17 371 SENIPLNTK 16 740 DVTDLGLHR 23 137 PLFPATVIN 17 380 IALITVTDK 16 130 EDINDNAPL 22 163 AVDPDVGIN 17 449 SAMLFIKVK 16 3 DINDNAPLF 22 177 ELIKSQNIF 17 504 LLGPDAPPE 16 177 ELIKSQNIF 22 S| EE DTYVMK IE R| GVPPLTSNV IEç H31 ENNSPGIQL |X 257 SIP_ENAPVG 17 608 SILDENDDF 16 477 ENNSPGIQL 22 E| QL ATDADI IE EI QESYTEY-VK IEH EjL IVPPSNCSY |E 290 !) NLVSNtARR ! R7l 700 AVDNDTGMN ==--LJ 381 ALITVTDKD 17 713 YSIVGGNTR 16 729 ETGNITLME 22 g| LLAADAGKP | | TLMEKCDVT| iI DTGEIFTTG 1 H| QL_KVSAMD |S m| DLGLHRVLV |E H| EVAILPDEI |E 503 YLL_GPDAPP 17 750 4VKANDLGQ 16 111 EVAILPDEI 21 4]) QLTKVSAMD ]) DLGLHRVLV) [l6 EVAiLPDEi 503 !) YLLGPDAPP ! [1 750J) LVKANDLGQjfl6 == =====H ===--LJ ==J--L 167) DVGiNGVQN 604 AVTLSiLDE F 761 SLFSVViVN F) 6 -iH 17- 624 AV-LSILDE 17 764 SVVIVNLFV 16 191 ETPEGDKMP 21 31 VIBPNLFD 1 SI SV_IVNLFV | | EVSIPENAP | 755 DLGQPDSLF 17 934 DLARHYKSA 16 8 ENAKIHFSF 21 765 WIVNLFVN 17 967 PLDNTFVAC 16 318 EETPNHKLL 21 769 NLFVN9SVT 17 366 DTWLSENI 1 779 ATLINELVR 17 Table XXVi-2$ STKEYAIKL 21 813 ILVAAVAGT 17 109P1 D4v. 1 693 TVVFQVIAV 21 17 ! t TabieXXV,- ! t] D4v. 1 pS A26-9-mers 806 PTSDYVKIL 21 821 TITVVVVIF 17 Each peptide is a 993 DCGYPVTTF 21 ifs GIgVSNTTF 17 portion of SEQ ID NO : 16 3 ; each start position is - PLIRIEEDT 96 Sppeplde is 9lam nof 368 WLSENIPL 20 161 peptide is 9 amino 391] F2 01 9 position for each F5 peptide is the start 555 TVFVSIIDQ 20 F161 position plus eight. 895 DVDSDGNRV 20 Table XXVI-Table XXVI-Table XXVI- 109P1 D4v. 1 109P1 D4v. 1 109P1 D4v. 1 A26-9-mers A26-9-mers A26-9-mers Each peptide is a Each peptide is a Each peptide is a portion of SEQ ID NO : portion of SEQ ID NO : portion of SEQ ID NO : 3 ; each start position is 3 ; each start position is 3 ; each start position is specified, the length of specified, the length of specified, the length of peptide is 9 amino peptide is 9 amino peptide is 9 amino acids, and the end acids, and the end acids, and the end position for each position for each position for each peptide is the start peptide is the start peptide is the start position plus eight. position plus eight. position plus eight. 931 DSPDLARHY 20 897 DSDGNRVTL 98 277 DIGENAKIH 15 83 EIFTTGARI 19 DLLSGTYIF 1 320 TPNHKLLVL 15 218 KVKVEDGGF 19 117 DEIFRLVKI 17 340 MVLVNVTDV 15 319 ETPNHKLLV 19 213 DTYVMKVKV 17 363 PVNDTVVLS 15 326 LVLASDGGL 19 350 DNVPSIDIR 17 367 TWLSENIP 15 533 EDKYLFTIL 19 372 ENIPLNTKI 17 470 FVTVSIPEN 15 715 IVGGNTRDL 19 431 EYAIKLLAA 17 471 VTVSIPENN 15 74 RVLVKANDL 19 578 YVPENLPRH 17 549 PLTSNVTVF 15 765 VVIVNLFVN 19 587 GTVGLITVT 17 567 SPVFTNNEY 15 809 DYVKILVAA 19 704 DTGMNAEVR 17 591 LITVTDPDY 15 23 TVWVIFIT 19 755 DLGQPDSLF 17 605 VTLSILDEN 15 825 WVIFITAV 19 822 ITVWVIFI 17 646 EDGGRVSRS 15 903 VTLDLPIDL 19 899 DGNRVTLDL 17 662 NWDVNDNK 15 953 ETPLNSKHH 19 GTYIFAVLL 16 671 PVFIVPPSN 15 11 AVLLACVVF 18 16 CVVFHSGAQ 16 774 ESVTNATLI 15 33 EMPENVLIG 18 17 WFHSGAQE 16 784 ELVRKSTEA |R 39 LIGDLLKDL 18 79 EDTGEIFTT 16 832 AVVRCRQAP 15 57 LTTAMQFKL 18 163 AVDPDVGIN 16 860 ENRQMIMMK 15 141 ATVINISIP 18 294 NIARRLFHL 16 877 SPKNLLLNF |E 142 TVINISIPE 18 529 DREKEDKYL 16 886 VTIEETKAD 15 168 VGINGVQNY 18 553 NVTVFVSII 16 902 RVTLDLPID 15 253 EIEVSIPEN 18 604 AVTLSILDE 16 958 SKHHIIQEL 15 356 DIRYIVNPV 18 614 DDFTIDSQT 16 1011 PVGIQVSNT 15 403 EIPFRLRPV 18 658 KVTINVVDV 16 458 DENDNAPVF 18 659 VTINVVDVN 16 Table XXVII-109P1D4 562 DQNDNSPVF 18 764 SVVIVNLFV 16 v. 1-B0702-9-mers 570 FTHNEYNFY 18 71 FVNESVTNA 16 Each peptide is a portion ofi SEQ ID NO : 68 STNPGTWF 18 799 EIADVSSPT 16 3 ; each start position is specific, the length of 694 VVFQVIAVD 18 810 YVI<ILVAAV 16 m| DQETGNITL |M Wil GTITVWVl acFds, and the end acids, and the end 763 FSWIVNLF 18 26 VVIFITAVV 16 position for each peptide is the start 821 TITVWVIF 18 976 DSISKCSSS 16 position plus eight. 824 WWIFITA 18 999 TTFEVPVSV 16 890 ETKADDVDS 18 211 EKDTYVMKV 15 583 LPRHGTVGL 25 Table XXVII-109P1D4 Table XXVII-109P1D4 Ta6le XXVI (-109P1D4 v. 1-B0702-9-mers v. 1-B0702-9-mers v. 1-B0702-9-mers Each peptide is a Each peptide is a Each peptide is a portion of SEQ ID NO : portion of SEQ ID NO : portion of SEQ ID NO : 3 ; each start position is 3 ; each start position is 3 ; each start position is specified, the length of specified, the length of specified, the length of peptide is 9 amino peptide is 9 amino peptide is 9 amino acids, and the end acids, and the end acids, and the end position for each position for each position for each peptide is the start peptide is the start peptide is the start position plus eight. position plus eight, position plus eight. I l I'I 362 NPVNDTVVL 24 262 APVGTSVTQ 16 599 1°GDNSAVTL 13 136 APLFPATVI | |AADAGKPPLIEg | SNCSYELVL | TPNHKLLVL 23 493 ADSGPNAKI 16 742 TDLGLHRVL 13 374 iPLNTKiAL 22 506 GPDAPPEFS 16 773 NESVTNATL 13 409 RPVFSNQFL 22 542 AKDNGVPPL 16 806 PTSDYVKIL 13 676 PPSNCSYEL 22 858 NPENRQMIM 16 817 AVAGTITVV 13 792 APVTPNTEI 22 875 KHSPKNLLL 16 839 APHLKAAQK 13 444 PPLNQSAML 21 897 DSDGNRVTL 16 899 DGNRV'fLDL 13 496 GPNAKINYL 21 907 LPIDLEEQT 16 940 KSASPQPAF 13 404 IPFRLRPVF 20 954 TPLNSKHHI 16 951 QPETPLNSK 13 52 IPNKSLTTA 19 31 REEMPENVL 15 960 HHIIQELPL 13 tel LPAAVDPDV 19 477 ENNSPGIQL 15 258 IPENAPVGT 19 507 PDAPPEFSL 95 Table XXVIII-109P1 D4 335 MPARAMVLV 19 715 IVGGNTRDL 15 v. 1-B08-9-mers 463 APVFTQSFV 19 948 FQIQPETPL 15 Each peptide is a portion of SEQ ID N0 : 758 QPDSLFSVV 19 1010 RPVGIQVSN 15 3 ; each start position is specified, the length of 115 LPDEIFRLV 18 100 IPRDEHCFY 14 226 FPQRSSTAI 98 154 INSKYTLPA 14 peptide is 9 amino acids, and the end 352 VPSIDIRYI 18 227 PQRSSTAIL 14 position for each peptide is the start 443 KPPLNQSAM 18 317 REETPNHKL 14 475 IPENNSPGI 18 509 APPEFSLDC 14 Position plus eight. 480 SPGtQLTKV 18 670 KPVFIVPPS 14 496 GPNAKINYL 28 548 PPLTSNVTV 18 738 KCDVTDLGL 14 43 LLKDLNLSL 27 686 LPSTNPGTV 18 762 LFSWIVNL 14 320 TPNHKLLVL 26 S|NPGTVVFQV|S B| KKHSPKNLL liN | FlKVKDEND |E 805 SPTSDYVKI 18 SGTYIFAVL 13 514 SLDCRTGML 26 m| SPKNLLLNF |R m| LSLIPNKSL 1D | GAQEKNYT, |E E|KPDSPDLAR|S E|WKTGDVPL|D R| HPVFKETEI |2 S| LPLDNTFVA |R | GARIDREKL |D R| STKEYAIKL |E EEl DPDVGINGV 1 m| EDINDNAPL |D m| SPKNLLLNF |E 246 HPVFKETEI 17 162 AAVDPDVGI 13 120 FRLVKIRFL 23 EDKYLFTIL 13 F R|DPDYGDNSA|S |TPEGDKMPQ|M m| PLNTKIALI |E E| TPNTEIADV |g E|PVGTSVTQL|D S| EDKYLFTIL |E S|TPNPENRQM|E S| EDKYLFTIL |S1 E|LPRHGTVGL|E Table XXVIII-109P1D4 Table XXVIII-109P1D4 Tabfe XXVIii-109P1D4 v. 1-B08-9-mers v. 1-B08-9-mers v. 9-B08-9-mers Each peptide is a Each peptide is a Each peptide is a portion of SEQ ID NO : portion of SEQ ID NO : portion of SEQ ID NO : 3 ; each start position is 3 ; each start position is 3 ; each start position is specified, the length of specified, the length of specified, the length of peptide is 9 amino peptide is 9 amino peptide is 9 amino acids, and the end acids, and the end acids, and the end position for each position for each position for each peptide is the start peptide is the start peptide is the start position pius eight, position plus eight. position plus eight. I I-I 41 GDLLKDLNL 22 124 KIRFLIEDI 9' 24 VFKETEIEV 14 66 VYKTCDVPL 22 218 KVI<VEDGGF 17 281 fAKiHFSFS 14 F307] NIARRLFHL 22 307 GLITIKEPL 17 283 KIHFSFSNL 14 '9551) FP-LNSKHHIIg F362 17 F3o8 88 GARIDREKL 21 409 RPVFSNQFL 17 352 VPSIDIRYI 14 736 MEKCDVTDL 21 426 YESTKEYAI 17 354 S1D1RYIVN 14 748 RVLVKANDL 21 676 PPSNCSYEt 17 403 EIPFRLRPV 14 866 MMKKKKKKK 21 839 APHLKAAQK 17 438 AADAGKPPL 14 867 MKKKKKKKK 21 1006 SVHTRPVGI 17 498 NAKINYLLG 14 | KKKKKKKKH | | SAINSKYTL |g | TILAKDNGV | 869 KKKKKKKNS 21 176 YELIKSQNI 16 792 APVTPNTEI 14 873 KKKNSPKNL 21 227 PQRSSTAIL 16 808 SDYVKILVA 14 875 KHSPKNLLL 21 310 TIKEPLDRE 16 858 NPENRQMIM 14 91 IDREKLCAG 20 313 EPLDREETP 16 880 NLLLNFVTI 14 193 PEGDKMPQL 20 405 PFRLRPVFS 16 958 SKHHIIQEL 14 845 AQKNKQNSE 20 444 PPLNQSAML 16 87Q KKKKKKHSP 20 633 REKQESYTF 16 Table XXIX-109P1D4 871 KKKKKHSPK 20 43 KAAQKNKQN 16 v. 1-81510-9-mers 927 TFKPDSPDL 2a 39 L1GDLLKDL 15 Each peptide is a portion of SEQ ID N0 : 416 FLLETAAYL 19 117 DEIFRLVKI 15 3 ; each start position is specified, the length of 631 FDREKQESY 19 178 LIKSQNIFG 15 peptide is 9 amino acids, and the end 114 ILPDEIFRL 18 433 AIKLLAADA 15 position for each - F5-4-11 peptide is the start position plus eight. 334 LMPARAMVL 18 805 SPTSDYVKI 15 S| IPLNTKIAL |E EIWRCRQAPH|Eç | KHSPKNLLL |W 451 MLFIKVKDE 18 864 MIMMKKKKK 95 300 FHLNATTGL 20 528 LDREKEDKY 18 51 LIPNKSLTT 14 960 HHIIQELPL 20 530 REKEDKYLF 18 119 IFRLVKIRF 14 391 DHNGRVTCF 18 ; E| SAKVTINVV 1EW 031 AINSKYTLP |S EEl ILPDEIFRL IEW ]) SAKVTiNVV) J18 j53] j AiNSKYTLP) [l4 iLPDE) FRL 18 VNDNKPVFI 18 970 INGVQNYEL 14 179 IKSQNlFGL 16 EITLMEKCDVTIE EEl ELIKSQNIF 1E E|VGGNTRDL|E H3|HLKAAQKNK|M E| LIVQKELDR IE ! SITDLGLHRVL|E HKLVYKTGDV VQKELDREE witDSDGNRVTL | VPLIRIEED IEY E| FPQRSSTAI f E| LVSNIARRL IE TableXXIX-1 PlD4 Table XXIX-1 09Pl DI Table XXX- v. 1-B1510-9-mers v. 1-B1510-9-mers 109P1D4v. 1- Each peptide is a Each peptide is a B2705-9-mers portion of SEQ ID NO : portion of SEQ ID NO : Each peptide is a 3 ; each start position is 3 ; each start position is portion of SEQ ID NO : specified, the length of specified, the length of 3 ; each start position is peptide is 9 amino peptide is 9 amino specified, the length of acids, and the end acids, and the end peptide is 9 amino position for each position for each acids, and the end peptide is the start peptide is the start position for each peptide position plus eight. position plus eight. is the start position plus eight. FTDHEIPFRL F3071 F394 I GRVTCFTDHI 24 FLFSVVIVNL FREETPNHKL] 12 104 EHCFYEVEV 14 334 LMPARAMVL 12 $1 NRQMIMM4CK 24 2Et FRLVKIRFL 14 404 IPFRLRPVF 12 408 LRPVFSNQF 23 170 INGVQNYEL 14 477 ENNSPGIQL 12 625 IRPNISFDR 23 FEETPNHKLLIH FFGPNAKINYLIH 362 NPVNDTVVL 14 497 PNAKINYLL 12 834 VRCRQAPHL 22 F374 IPLNTKIAL 14 520 GMLTVVKKL 12 41 GDLLKDLNL 29 401 DHEIPFRLR 94 529 DREKEDKYL 12 9 DREKLCAGI 20 m| PDAPPEFSL | EXTHNEYNFYV|g E| KMPQLlVQK | 599 YGDNSAVTL 14 575 YNFYVPENL 12 633 REKQESYTF 20 717 TNATLINEL 14 602 NSAVTLSIL 12 901 NRVTLDLPI 20 m | T F K P D S P D L | E E | D V N D N K P V F | E m | L N L S L I P N K 1 S 927 TFKPDSPDL 14 665 DVNDNKPVF 12 47 LNLSLIPNK 19 6 GTYIFAVLL 13 676 PPSNCSYEL 12 304 ATTGLITIK 19 66 VYKTGDVPL 13 678 SNCSYELVL 12 520 GMLTWKKL 19 EEl FYEVEVAIL 13 754 NDLGQPDSL 12 84 PRNGTVGLI 19 EE|PEGDKMPQL|D H|KKHSPKNLL|S | GVIRPNlSF |S 245 NHPVFKETE 13 903 VTLDLPIDL 12 748 RVLVKANDL 19 E| TPNHKLLVL 13 948 FQIQPETPL 12 75 IRIEEDTGE 18 429 TKEYAIKLL 13 958 SKHHIIQEL 12 177 ELIKSQNIF 18 438 AADAGKPPL 13 1007 VHTRPVGIQ 12 29 RRLFHLNAT 18 542 AKDNGVPPL 13 a 317 REETPNNKL 18 583 LPRNGTVGL 13 496 GPNAKINYL 18 EEl STNPGTWF 13 Tabfe XXX-535 KYLFTILAK 18 Fl o7 DQETGNiTL B2705-9-mers = Q-rYiFAVi L F746] FLHRVLV [N Each peptide is a F31 773 NESVTNATL 13 portion of SEQ ID N0 : REEMPENVL 17 806 PTSDYVKIL 13 3 ; each start position is 55 KSLTTAMQF 17 5 SGTYIFAVL 12 specified, the length of 114 ILPDEIFRL 17 peptide is 9 amino acids, and the end 119 IFRLVKIRF 17 | PENVLIGDL |g position for each peptide 35 PENvUGDL 12'.,.....'-- 12 is the start position plus F3071 E31 SAINSKYTL 1 E| ITIKEPLDR |g ! iHFSFSNLV12) ''' 0 Table XXX-Table XXX-Table XXX- 109P1 b4v. 1- 109P1 D4v. 1- 109P1 D4v. 1- B2705-9-mers B2705-9-mers B2705-9-mers Each peptide is a Each peptide is a Each peptide is a portion of SEQ ID NO : portion of SEQ ID NO : portion of SEQ ID NO : 3 ; each start position is 3 ; each start position is 3 ; each start position is specified, the length of specified, the length of specified, the length of peptide is 9 amino peptide is 9 amino peptide is 9 amino acids, and the end acids, and the end acids, and the end position for each peptide position for each peptide position for each peptide is the start position plus is the start position plus is the start position plus eight. eight. eight. l l 404 IPFRLRPVF 17 835 RCRQAPHLK 16 416 FLLET"nAAYL 5 E RPVFSNQFL 17 839 APHLKAAQK 16 42 P, YLDI°ESTP< 5 479 NSPGIQLTK 17 860 ENRQMIMMK 16 428 STKEYAIKL 15 | RTGMLTWK |i | RQMIMMKKK | | MDAGKPPL |g 530 REKEDKYLF 17 866 MMKKKKKKK 16 445 PLNQSAMLF 15 645 AEDGGRVSR 17 867 MKKKKKKKK 16 449 SAMLFIKVK 15 649 GRVSRSSSA 17 868 KKKKKKKKH 16 497 PNAKINYLL 15 S| RVSRSSSAK IE E| KKKKKHSPK |E B| TGMLTWKK IEffl 747 HRVLVKAND 17 875 KHSPKNLLL 16 524 VVKKLDREK 1S 762 LFSVVIVNL 17 940 KSASPQPAF |E H| AKDNGVPPL IEç '780 TL1NELVRK 17 1009 TRPVGIQVS 16 577 FYVPENLPR t (l5 865 IMMKKKKKK 17 DLLSGTYIF 15 662 NVVDVNDN4C 15 948 FQIQPETPL 17 23 AQEKNYTIR 15 688 STNPGTWF |E 964 QELPLDNTF 17 49 LSLlPNKSL 15 727 DQETGNITL 15 11 AVLLACWF 16 82 GEIFTTGAR 95 728 QETGNlILM 15 37 NVLIGDLLK 16 88 GARIDREKL 15 744 LGLHRVLVK 15 125 IRFLIEDIN 16 112 VAILPDEIF 15 754 NDLGQPDSL 95 152 SAINSKYTL 16 113 AILPDEIFR 15 755 DLGQPDSLF 15 179 IKSQNIFGL 16 118 EIFRLVKIR 15 779 ATLINELVR 15 199 PQLIVQKEL 6 149 PENSAINSK 15 820 GTITVWVI 15 Sil REEKDTYVM 16 968 VGINGVQNY 15 863 QMIMMKKKK 15 221 VEDGGFPQR 16 201 LIVQKELDR 15 873 KKKHSPKNL 15 276 ADIGENAKI 16 208 DREEKD'TYV 15 874 KKHSPKNLL 15 283 KIHFSFSNL 16 263 PVGTSVTQL 15 877 SPKNLLLNF 15 337 ARAMVLVNV 16 289 SNLVSNIAR 15 894 DDVDSDGNR 15 350 DNVPSIDIR 16 296 ARRLFHLNA 15 929 KPDSPDLAR 15 F3-8 IALlTVTDK 6 332 GGLMPAIAM 15 936 ARHYKSASP 15 435 KLLAADAGK |E 368 VVLSENIPL 15 958 SKHHI1QEL 15 517 CRTGMLTVV 16 372 ENIPLNTKI 15 993 DCGYPVTTF 15 575 YNFYVPENL 16 374 IPLNTKIAL 15 18 VFNSGAQEK 14 793 YSIVGGNTR 16 391 DHNGRVTGF 15 22 GAQEKNYTI 14 742 TDLGLHRVL 16 399 FTDHEIPFR 15 26 KNYTIREEM 14 777 TNATLINEL 16 4Q6 FRLRPVFSN 15 30 IREEMPENV 14 827 VIFITAVVR 16 490 PVFSNQFL. 15 35 PENVLIGDL 14 Table XXX-Table XXX-Table XXX- 109P1D4V. 1- 109P1D4V. 1- 109P1D4v. 1- B2705-9-mers B2705-9-mers B2705-9-mers Each peptide is a Each peptide is a Each peptide is a portion of SEQ ID NO : portion of SEQ ID NO : portion of SEQ ID NO : 3 ; each start position is 3 ; each start position is 3 ; each start position is specified, the length of specified, the length of specified, the length of peptide is 9 amino peptide is 9 amino peptide is 9 amino acids, and the end acids, and the end acids, and the end position for each peptide position for each peptide position for each peptide is the start position plus is the start position plus is the start position plus eight. eight. eight. l l | LLKDLNLSL {Et FSVVlVNLF lii g|DADSGPNAKW mil LTTAMQFKL IEi | SSPTSDYVK {Ei | PDAPPEFSL {Eg 60 AMQF6CLVYK 14 836 CRQAPHLKA 14 533 EDKYLFTIL 13 66 VYKTGDVPL 14 841 HLKAAQKNK 14 562 DQNDNSPVF 13 68 KTGDVPLIR 14 864 MIMMKKKKK 14 569 VFTHNEYNF 13 121 RLVKIRFLI 94 897 DSDGNRVTL 14 578 YVPENLPRH 13 130 EDINDNAPL 14 903 VTLDLPIDL 14 583 LPRNGTVGL 13 | APLFPATVI liS E|NWVTTPTTF|E | GTVGLITVT i 170 INGVQNYEL 14 951 QPETPLNSK 14 639 FDREKQESY 13 172 GVQNYELIK 14 952 PETPLNSKH 14 632 DREKQESYT 13 212 KDTYVMKVK 14 a SGTYIFAVL 13 652 SRSSSAKVT 13 E|KVKVEDGGF|-S X| ENVLIGDLL |S E| RSSSAKVTI liM 280) ENAKIHFSF lE XI TAMQFKLVY lE I DVNDNKPVF lDE 291 LVSNIARRL 14 85 FTTGARIDR 13 674 IVPPSNCSY 13 300 FHLNATTGL 14 87 TGARIDREK 13 676 PPSNCSYEL 320 TPNHKLLVL 14 89 ARIDREKLC 13 699 IAVDNDTGM 13 326 LVLASDGGL 14 94 EKLCAGIPR 13 715 IVGGNTRDL 13 330 SDGGLMPAR 14 99 GIPRDEHCF 13 720 TRDLFAIDQ 13 379 SENIPLNTK 14 107 FYEVEVAIL 13 730 TGNITLMEK 13 400 TDHEIPFRL 94 146 ISIPENSAI 13 736 MEKCDVTDL 13 427 ESTKEYAIK 14 150 ENSAINSKY 13 773 NESVTNATL 13 443 KPPLNQSAM 14 190 IETPEGDKM 13 792 APVTPNTEI 13 444 PPLNQSAML 14 193 PEGDKMPQL 13 821 TITWVVIF 13 483 IQLTKVSAM 14 275 DADIGENAK 13 854 WATPNPENR 13 493 ADSGPNAKI 14 278 IGENAKIHF 13 884 NFVTIEETK 13 M| LTWKKLDR 14 315 LDREETPNH 13 921 WVTTPTTFK 13 527 KLDREKEDK 14 334 LMPARAMVL 13 927 TFKPDSPDL 13 | PLTSNVTVF | 31 NVPSIDIRY lii | PDSPDLARH IEi 599 YGDNSAVTL 14 362 NPVNDTVVL 13 960 HHIIQELPL 13 608 SILDENDDF 14 415 QFLLETAAY 13 972 FVAGDSISK 13 | IDSQTGVIR IEM | LDYESTKEY 13 1002 EVPVSVHTR 13 627 PNISFDREK 14 429 TKEYAIKLL 13 711 VRYSIVGGN 14 458 DENDNAPVF 93 TabIeXXXI-109P1D4v, 1 '738lu KCDVTDLGL 14 477 ENNSPGIQL 13 82709-9-mers Each peptide is a Table 109P1D4v. 1 Table XXXI-109PID4v. l portion of SEQ ID NO : B2709-9-mers B2709-9-mers 3 ; each start position is Each pepSide is a Each peptide is a specified, the length of portion of SEQ ID NO : portion of SEQ ID NO, peptide is 9 amino 3 ; each start position is 3 ; each start position is acids, and the end specified, the length of specified, the length of position for each pep Me ,,, g , 3 J,, is the start position plus acids, and the end acids, and the end eight. position for each peptide position for each peptide is the start position plus is the start position plus IF20IF-FRLVKIRFL 2n2 '834')) VRCRQAPHL 22 337 RRAMVLVNV 21 76 RVEpTCEI 13 136 P, PLFPATVI 12 30 fREEMPENV 20 102 RDEHCFYEV 13 152 SAINSICI°TL 12 529 DREKEDKYL 20 250 KETEIEVSI 13 170 INGVQNYEL 92 901 NRVf'LDLPI 20 283 KIHFSFSNL 13 193 PEGDKMPQL 12 408 LRPVFSNQF 19 29 LVSNIARRL 13 195 GDKMPQLIV 12 517 CRTGMLTW 19 296 ARRLFHLNA 13 199 PQLIVQKEL 12 584 PRHGTVGLI 19 362 NPVNDTVVL 13 228 QRSSTAILQ 12 F5874 19 F3621 F2281 F786 DREKLCAGI 18 374 IPLNTK1Al. 13 284 1HFSFSNLV 12 208 DREEKDTYV 18 406 FRLRPVFSN 13 300 FHLNATTGL 12 GTYIFAVLL 17 410 PVFSNQFLL 13 318 EETPNHKLL 12 41 GDLLKDLNL 17 416 FLLETAAYL 13 326 LVLASDGGL 12 748 RVLVKANDL 17 496 GPNAKINYL 13 333 GLMPARAMV 12 297)) RRLFHLNAT 16 542 AKDNVPPL 13 A00 TDHEIPFRL 12 520 GMLTVVKKL 16 546 GVPPLTSNV 13 A04 IPfRLRPVF 12 307)) GLITIKEPL 15 575 YNFYVPENL 13 438 AADAGKPPL 12 409 RPVFSNQFL 5 633 REKQESYTF 13 444 PPLNQSAML 12 649 GRVSRSSSA 15 65 KVTfNVVDV 13 47 ENNSPGIQL 12 711 VRYSIVGGN 15 7$ GNTRDLFAI 13 483 IQLTKVSAM 12 31 REEMPENVL 14 738 KCDVTDLGL 13 497 PNAKINYLL 12 m| KSLTTAMQF | m| KKKHSPKNL |g S| YGDNSAVTL |g X| GARIDREKL |S B| KKHSPKNLL 13 623 GVIRPNISF 12 121 RLVKIRFLI 14 927 TFKPDSPDL 13 625 IRPNISFDR 12 125 IRFLIEDIN 14 d-SnIF 12 652 SRSSSAKVT 12 E|REEKDTYVM|S m| SGTYIFAVL |g E| SNCSYELVL |S 229 RSSTAVLQV 14 11 AVLLACWF 12 736 MEKCDVTDL 12 E| REETPNHKL | m| GAQEKNYTI | R| TDLGLHRVL | |GGLMPARAM|S X| ENVLIGDLL |g m| WRVLVKAND |R 357 IRYVVNPVN 14 49 LSLIPNKSL 2 754 NDLGQPDSL 12 GRVTCFTDH 14 67 YKTGDVPLI 12 760 DSLFSWIV 12 530 REKEDKYLF 14 75 IRIEEDTGE 12 762 LFSVVIVNL 12 E31 RSSSAKVTI |E S| ARIDREKLC |S E| SPTSDYVKI |S 820 GTITWVVI 14 99 GIPRDHCF 12 819 AGTITVVVV 12 875 KHSPKNLLL 14 114 fLPDEiFRL 12 903 VTLDLPIDL 12 26 KNYTIREEM 13 3 EDINDNAPL 12 940 KSASPQPAF 12 Table XXXI-109P1 D4v. 1 Table XXXI-109P1 D4v. 1 Table XXXII-109P1 D4 B2709-9-mers B2709-9-mers v. 1-B4402-9-mers Each peptide is a Each peptide is a Each peptide is a portion of SEQ ID NO : portion of SEQ tD NO : portion of SEQ ID NO : 3 ; each start position is 3 ; each start position is 3 ; each start position is specified, the length of specified, the length of specified, the length of peptide is 9 amino peptide is 9 amino peptide is 9 amino acids, and the end acids, and the end acids, and the end position for each peptide position for each peptide position for each is the start position plus is the start position plus peptide is the start eight. eight. position plus eight. E| HHIIQELPL |S |GQPDSLFSV|E S| PENVLIGDL g @I LLKDLNLSL IE E| FSWIVNLF IE Ej|REETPNHKL|g 57 LTTAMQFKL 11 806 PTSDYVKIL 11 773 NESVTNATL 23 64 6CLVYKTGDV 11 821 TITVWVIF 11 31 REEMPENVL 22 66 VYKTGDVPL 11 822 ITVWVIFI 11 193 PEGDKMPQL 22 83 EIFTTGARI 11 836 GRQAPHLKA 11 426 YESTKEYAI 22 106 CFYEVEVAI 11 861 NRQMIMMKK 11 532 KEDKYLFTI 22 E3 FYEVEVAIL 11 880 NLLLNFVTI 11 77 IEEDTGEIF 21 146 ISIPENSAl IE Ej|DVDSDGNRV|E W| KETEIEVSI |E 162 AAVDPbVGI 11 897 DSDGNRVTL 11 418 LETAAYLDY 21 EI YELIKSQNI IE 31 DGNRVTLDLIE W| REKEDKYLF |E 179 IKSQNIFG 11 936 ARHYKSASP 11 633 REKQESYTF 21 190 IETPEGDKM 11 942 ASPQPAFQI 11 736 MEKCDVTDL 21 213 DTYVMKVKV 11 948 FQIQPETPL 11 911 LEEQTMGKY 21 227 PQRSSTAIL 11 958 SKHHIIQEL 11 176 YELIKSQNI 19 320 TPNHKLLVL 11 964 QELPLDNTF 11 402 HEIPFRLRP 18 334 LMPARAMVL 11 983 SSSSDPYSV 11 11 AVLLACVVF 17 340 MVLVNVTDV 91 995 GYPVTTFEV 11 372 ENIPLNTKI 17 353 PSIDIRYIV 11 999 TTFEVPVSV 11 645 AEDGGRVSR 17 388 KDADHNGRV 11 9013 GIQVSNTTF 11 688 STNPGTVVF 17 F, 11 rl 76] 457 KDENDNAPV 11 Table XXXII-109P1D4 82 GEIFTTGAR 16 507 PDAPPEFSL 11 v. 1-84402-9-mers 130 EDINDNAPL 16 548 PPLTSNVTV 11 Each peptie is a 146 ISIPENSAI 16 portion of SEQ ID N0 : SI PLTSNVTVF IE 3 ; each start position is 152 SAINSKYTL 1 specified, the length of 16 F569 peptide is 9 amino acids, and the end XI LPRHGTVGL IE position for each 597 PDYGDNSAV 11 peptide is the start 520 GMLTVVKKL 16 621 QTGVIRPNI 11 position plus eight. OO 542 AKDNGVPPL 16 635 KQESYTFYV 11 3Tg EETPNNKLL 29 709 AEVRYSIVG 16 | PPSNCSYEL | | EEMPENVLI |g | QETGNITLM 1S F, 11 9F6 41 715 IVGGNTRDL 11 g64 QELPLDNTF 26 $97 DSDGNRVTL 16 EI TRDLFAIDQ IEI EgLDEIFRLVKI 1E | ENVLIGDLL 1 E11 ITLMEKCDV IE 03|DENDNAPVF|E W|KSLTTAMQF1R Table XXXIi-109P1D4 Table XXXil1i-109P1D4 Tabie XXXIIIi-109P1D4 v. 1-B4402-9-mers v. 1-B5101-9-mers v. 1-B5101-9-mers Each peptide is a Each peptide is a Each peptide is a portion of SEQ ID NO : portion of SEQ ID NO : portion of SEQ ID NO : 3 ; each start position is 3 ; each start position is 3 ; each start position is specified, the length of specified, the length of specified, the length of peptide is 9 amino peptide is 9 amino peptide is 9 amino acids, and the end acids, and the end acids, and the end position for each position for each position for each peptide is the start peptide is the start peptide is the start position plus eight. position plus eight. position plus eight. 78 EEDTGEIFT 5 303 NATTGLfTI 6 1Q6 CFYEVEVAI 19 114 iLPDEIFRL 15 548 PPLTSNVTV 26 152 SAiNSKYTL 9 120 FRLVKIRFL 15 954 TPLNSKHHI 25 194 EGDKMPQLI 19 129 IEDINDNAP 95 115 LPDEIFRLV 24 463 APVFTQSFV 19 150 ENSAINSKY 15 165 DPDVG1NGV 24 583 LPRHGTVGL 19 168 VGINGVQNY 15 656 SAKVTINVV 24 599 YGDNSAVTL 19 179 IKSQNIFGL 15 66 LPSTNPGTV 24 708 NAEVRYSIV 99 205 KELDREEKD 15 690 NPGTVVFQV 24 820 GT1TWVVI 19 291 LVSNIARRL 15 818 VAGTITVVV 24 899 DGNRVTLDL 19 307 GLITIKEPL 15 10 FAVLLACVV 23 52 IPNKSLTTA 18 iS| NPVNDTVVL |S R| NAPLFPATV |g I GARIDREKL lii B| IPLNTKIAL |g S|LPMVDPDV|X B| DEIFRLVKI |M 404 IPFRLRPVF 15 226 FPQRSSTAI 23 138 LFPATVINI 18 H| QFLLETAAY |S w| TPNHKLLVL |X E|PARAMVLVN|S 599 YGDNSAVTL 15 352 VPSIDIRYI 23 380 IALITVTDK 18 599ttYGDNSAVTLtl5 3521 (VPSiDiRY ! [23 380') tALtTVTDK (fl8 623 GVIRPNISF 15 792 APVTPNTEI 23 389 DADHNGRVi'18 762 LFSWIVNL 15 805 SPTSDYVKI 23 409 RPVFSNQFL 18 777 TNATLINEL 15 140 PATVINISI 22 444 PPLNQSAML 18 806 PTSDYVKIL 15 162 AAVDPDVGI 22 586 HGTVGLITV 18 820 GTiTVWVI 15 246 NPVFKETEI 22 601 DNSA1/TLSI 18 iHll NLLLNFVTI lS E| IPLNTKIAL |W E| DSLFSVVIV |S 912 EEQTMGKYN 15 475 IPENNSPGI 22 814 LVAAVAGTI 18 958 SKHHIIQEL 15 480 SPGIQLTKV 22 966 LPLDNTFVA 18 E| PGTVVFQVI 22 Sl YPVTTFEVP lS TabIeXXXllil-109P1D4 758 QPDSLFSW 22 171 NGVQNYELI 17 v. 1-85101-9-mers 816 AAVAGTITV 22 347 DVNDNVPSI 17 Each peptide is a Each of SEQ ID N0 : 362 NPVNDTVVL 21 438 AADAGKPPL 97 portion of SEQ iD NO :---F= L-JL-L 3 ; each start position is 795 TpNTEIADV 21 440 DAGKPPLNQ 17 specified, the length of 819 AGTITVVVV 21 547 VPPLTSNVT 97 peDtideis9amino F=-=ir r-r peptide is 9 amino 6g T ( ; pVPI. IRI 20 22 ITVVVVIFI 17 acids, and the end F691- position for each 213 DTYVMKVKV 20 880 NLLLNFVTI 17 peptide is the start 20 ln6 position plus weight. 496 GPNAK1NYL 20 139 FPATVIN1S 16 12 APLFPATVt 27 778 NATLINELV 20 208 DREEKDTYV 16 ES, APLFPATVI l |DPYSVSDCG|E | TAILQVSVT |g Table XXXI111-109P1 D4 Table XXXIIII-109P1 D4 Table XXXIIII-109P1 D4 v. 1-B5101-9-mers v. 1-B5101-9-mers v. 1-B5101-9-mers Each peptide is a Each peptide is a Each peptide is a portion of SEQ ID NO : portion of SEQ ID NO : portion of SEQ ID NO : 3 ; each start position is 3 ; each start position is 3 ; each start position is specified, the length of specified, the length of specified, the length of peptide is 9 amino peptide is 9 amino peptide is 9 amino acids, and the end acids, and the end acids, and the end position for each position for each position for each peptide is the start peptide is the start peptide is the start position plus eight. position plus eight. position plus eight. . I 1 11 338 RAMVLVNVC 16 00 IADVSSPTS 15 742 TDLGLHRVL 14 H| IPFRLRPVF |g E| AVAGTITVV |g E| PDSLFSVVI |E 492 DADSGPNAK 16 1003 VPVSVHTRP 15 76 VNLFVNESV 14 508 DAPPEFSLD 16 30 IREEMPENV 14 895 DVDSDGNRV 14 516 DCRTGMLTV 16 72 VPLIRIEED 4 897 DSDGNRVTL 14 520 GMLTWKKL 16 83 EIFTTGARI 14 676 PPSNCSYEL 16 156 SKYTLPAAV 14 Table XXXIV-109P1D4 744 LGLHRVLVK 16 161 PAAVDPDVG 14 v. 1-A1-10-mers 791 EAPVTPNTE 16 182 QNIFGLDVI 14 Each peptide is a portion of SEQ ID N0 : 973 VACDSISKC 16 211 EKDTYVMKV 14 3 ; each start position is specified, the length of 16 specified, the length of 1 MDLLSCTYI 15 276 ADIGENAKI 14 peptide is 10 amino acids, and the end 14 LACVVFHSG 15 328 LASDGGLMP 14 position for each peptide is the start position plus nixe. 31 TAMQFKLVY 15 340 MVLVNVTDV 14 F6 7 F361] 67 YKTGDVPLI 15 361 VNPVNDTVV 14 47 LLETAAYLDY 32 q) DREKLCAGI 95 366 DTVVLSEN ! 14 5g TTAMQFKLVY 28 148 IPENSAINS 15 372 ENIPLN'fKl 14 q, 3 YLDYEST_KEY 28 031 YELIKSQNI 15 H| AAYLDYEST 14 527 KLDREKEDKY 28 185 FGLDVIETP |g | YESTKEYAI 14 910 DLEEQTMGKY 28 031 MPQLIVQKE |g g| YAIKLLAAD |E H| D_GPNAKINY} E 261 NAPVGTSVT 15 437 LAADAGKPP 14 630 SF_DREKgESY 27 262 APVG'SVTQ 15 465 VFTQSFVTV 14 206 EL_DREEKDTY 26 E| DADIGENAK r N F597] F | EPLDREETP | g| ADSGPNAKI |i E|VTDPDYGDNS|E 356 DIRYIVNPV 15 509 APPEFSLDC 14 673 FIVPPSNCSY 21 ) iVNPVNDTV TiLAKDNGV TODTGMNAEVRY 449 SAMLFIKVK 15 541 LAKDNGVPP 14 807 TSDYVKILVA 21 E| GRTGMLTVV 15 579 VPENLPRHG 14 gg SSDPYSVSDG 21 X| KEDKYLFTI |S SI PRHGTVGLì IE S|AiDPDVGING |E M| SNVTVFVSI |S E|PDYGDNSAV|S E| E_EIEVSIPE |X JDPDYGDNSA H|KAEDGGRVS|S M| TIDSQTGVI |S H|PDSPDL_RHY|S MNAEVRYS VNDNKPVH LPDEiFRLVK | DQETGNITL |g | IAVDNDTGM |i | PENSAINSKY |g Table XXXIV-109P1D4 Table XXXV-109P1D4 Table XXXV-109P1D4 v. 1-A1-10-mers v. 1-A0201-10-mers v. 1-A0201-10-mers Each peptide is a Each peptide is a portion Each peptide is a portion portion of SEQ ID NO : of SEQ ID NO : 3 ; each of SEQ ID NO : 3 ; each 3 ; each start position is start position is start position is specified, the length of specified, the length of specified, the length of peptide is 10 amino peptide is 10 amino peptide is 10 amino acids, and the end acids, and the end acids, and the end position for each peptide position for each peptide position for each peptide is the start position plus is the start position plus is the start position plus nine. nine nine S|V_DTNDNHPV|E | VLIGDLLKDL |E Sil LiPNKSLTTA |X S11 ATDADIGENP, 1 113 R, ILPDEIFRL 28 60 P, MQFKLVYi<T 20 B|V_DVNDNVPS|M | YIFAV_LACV | | AILQVSVTDT 1E 4F2911 TKEYAIKLLA l8 169 GINGVCNYEL 25 290 NLVSNIARRL 20 SLV_DLGLHRVL|M | DLLKDLNLSL 24 428 STKEYAIKLL 20 789 STEAPVTPNT 18 43 LLKDLNLSLI 24 437 LAADAGKPPL 20 897 DSDGNRVTLD 18 178 LIKSQNIFGL 24 560 IIDQNDNSPV 20 19 FHSGAQEKNY 17 333 GLMPARAMVL 24 692 GTWFCVIAV 20 107 FYEVEVAILP 17 339 AMVLVNVTDV 24 756 LGQPDSLFSV 20 385 VTDKDADHNG 17 609 ILDENDDFTI 24 816 AAVAGTITW 20 399 FTDHEIPFRL 17 50 SLIPNKSLTT 23 824 VVVVIFITAV 20 401] DHEIPFRLRP 17 56 SLTTAMQFKL 23 962 IIQELPLDNT 20 797 NTEIADVSSP 17 114 ILPDEIFRLV 23 65 LVYKTGDVPL 19 904 TLDLPIDLEE 17 325 LLVLASDGGL 23 106 CFYEVEVAIL 19 H| IGDLLKDLNL 16 582 NLPRHGTVGL 23 127 FLIEDINDNA 19 44 LKDLNLSLIP 16 685 VLPSTNPGTV 23 257 SIPENAPVGT 19 167 DVGINGVQNY 16 735 LMEKCDVTDL 23 283 KIHFSFSNLV 19 194 EGDKMPCLIV 16 776 VTNATLINEL 23 355 IDIRYIVNPV 19 329 ASDGGLMPAR 16 137 PLFPATVINI 22 360 IVNPVNDTVV 19 514 SLDCRTGMLT 16 334 LMPARAMVLV 22 373 NIPLNTKIAL 19 F5691 VFTHNEYNFY 16 359 YIVNPVNDTV 22 538 FTILAKDlGV 19 590 GLITVTDPDY 16 474 SIPENNSPGI 22 655 SSAKVTINW 19 801 ADVSSPTSDY 16 714 SIVGGNTRDL 22 767 IVNLFVNESV 19 812 KILVAAVAGT 22 815 VAAVAGTITV 19 Table XXXV-109P1 D4 813 ILVAAVAGTI 22 821 TITVWVIFI 19 v. 1-A0201-10-mers 817 AVAGTITVW 22 887 TIEETKADDV 19 Each peptide is a portion gg2 LLNFVTIEET 22 68 KTGDVPLIRI 18 of SEQ ID N0 : 3 ; each- start position is 48 NLSLIPNKSL 21 164 VDPDVGINGV 18 specified, the length of 159 TLPAAVDPDV 21 262 APVGTSVTQL 18 peptide is 10 amino 1 ! ! Mr ! n\/ !) =T ! r ? ? <-, mti QM ! ARR ! pH) peptide is 10 amino g3 NIFGLDVIET 21 293 SNIARRLFHL 18 amids, and the end 0-0 position for each peptide 541 LAKDNGVPPL 21 302 LNATTGLITi 18 is the start position plus-1 F 118 nine 794 VTPNTEIADV 21 374 IPLNTKIALI 18 m| LLSGTYIFAV 29 88 VAGTITVVW 21 42 HEIPFRLRPV 18 761 SLFSVVIVNL 29 29 TIREEMPENV 20 479 NSPGIQLTKV 18 Table XXXV-109P1 D4 Table XXXV-109P1 D4 Table XXXV-109P1 D4 v. 1-A0201-10-mers v, 1-A0201-1 -mers v. 1-A0201-10-mers Each peptide is a portion Each peptide is a portion Each peptide is a portion of SEQ of SEQ ID NO : 3 ; each of SEQ ID NO : 3 ; each start position is start position is start position is specified, the length of specified, the length of specified, the tength of peptide is 10 amino peptide is 10 amino peptide is 10 amino acids, and the end acids, and the end acids, and the end position for each peptide position for each peptide position for each peptide is the start position plus is the start position plus is the start position plus nine nine nine 42 GIQLT4<VSAM 18 464 PVFTQS_FVTV 16 230 SSTAILQVSV 15 F54-9] PLTSNVTVFV 18 514 SLDCRT_CMLT 16 265 GTSVTQLHAT 15 650 RVSRSSSAKV 18 599 TGMLTWKKL 16 275 DADIGENAKI 15 zen AKVTINVVDV | 1 ILAKDNGVPP |g |LASDGGLMPA|M 740 DVTDLGLHRV 18 559 SIIDQNDNSP 16 332 GGLMPARAMV 95 780 TLINELVRKS 18 585 RHGTVGLITV 16 346 TDVNDNVPSI 95 |il LINELVRKST 18 616 FTIDSQ_TGVI 16 379 KIALITVTDK 15 785 LVRKSTEAPV 18 684 LVLPSTNPGT 16 399 FTDHEIPFRL l5 12 VLLACVVFHS 17 689 TNPGTV_VFQV 16 435 KLLAADAGKP 15 ILLACVVFHSG-I VIAVD F-IVKDENANAPV 134 DNAPLFPATV 97 724 FAIDQETGNI 16 490 AMDADSGPNA 15 145 NISIPENSAI 17 726 IDQETG_NITL 16 492 DADSGPNAKI 15 336 PARAMVLVNV FP 742 TDLGLHRVLV 16 515 LDCRTGMTV 15 376 LNTKIALITV 17 744 LGLHRVLVKA 16 547 VPPLTSNVTV 15 Zll ALITVT_DKDA 17 766 VIVNLFVNES 16 570 FTHNEYNFYV 15 445 PLNQSAMLFI 17 809 DYVKILVAAV 16 642 YVKAEDGGRV 15 466 FTQSFVTVSI 17 827 VIFITA_VVRC 16 665 DVNDNKPVFI 15 F495l SGPNAKINYL 17 833 VVRCRQ_APHL 16 666 VNDNKPVF1V 15 503)) YLLGPDAPPE 17 877 SPKNLLLNFV 96 688 STNPGTVVFQ 15 fol LLGPDAPPEF 17 880 NLLLNFVTIE 16 717 GGNi'RDLFAI 15 608 SILDENDDFT 7 881 LLLNFV_TIEE 16 725 AIDQETGNIT 15 M| NITLMEKCDV 17 896 VDSDGNRVTL 16 741 VTDLGLHRVL 15 734 TLMEKCDVTD 17 915 TMGKYN_WVTT 16 745 GLHRVLVKAN I 15 825 WVfFITAVV 17 926 TTFKPD_SPDL 16 769 NLFVNESVTN 15 998 VTTFEVPVSV 17 941 SASPQP_AFQI 16 819 AGTlTWVVI 15 75 IRIEEDTGEI 16 2 DLLSGT_YIFA 15 879 KNLLLNFVTI 15 119) (KIRFL I GTYIF8VLLA INSKHHIIQELI 153 AINSKYTLPA 16 21 SGAQE6_<NYTI 15 982 SSSSSDPYSV 15 231 STAILC, VSVT 16 46 DLNLSLIPNK 15 994 CGYPVTTFEV 15 239 VTDTNDNHPV 16 91 IDREKLCACI 15 30 HLNATTGLIT 16 123 VK1RFLIEDI 15 TabIeXXXVI-109P1D4 F3,-gl ETPNHKLLVL 16 151 NSAiNSKYTL 15 v. 1-A0203-10-mers 351 NVPSIDIRYI 16 181 SQNIFG_LDVI 15 354) SIDIRYIVNP 16 197 KMPQLIVQKE 15 Eg FLLETAAYLD 16 228 QRSSI'A_ILQV 15 Each peptide is a portion Table XXXVI-109P1 D4 Table XXXVI-109P1 D4 of SEQ ID NO : 3 ; each v. 1-A0203-10-mers v. 1-A0203-10-mers start position is start position is Each peptide is a portion Each peptide is a portion specified, the length of of SEQ ID NO : 3 ; each of SEQ ID NO : 3 ; each peptide is 10 amino start position is start position is acids, and the end specified, the length of specified, the length of position for each peptide peptide is 10 amino peptide is 10 amino is the start position plus acids, and the end acids, and the end position for each peptide position for each peptide is the start position plus is the start position plus ES| INSKYTLPAA 19 nine nine 413 SNQFLLETAA 19 H11 KEYAIK-LAA 1 H| TKEYAIKLLA |E I L ! EDINDNAp 1E | SDYVKILVM | HIAGKPPLNQSA | | NDNAPLEPAT | 836 CRQAPHLKAA | | I_VKDENDNA |g | N ! SIPENSAI | 330 SDGGLMPARA 18 481 PGIQLTKVSA 10 225 GFPQRSSTAI 9 432 YAIKLLAADA 188 84 QLTKVSAMDA 10 254 IEVSIPENAP 9 810 YVKILVAAVA 18 490 AMDADSGPNA 10 265 GTSVTQLHAT 9 E31 NSKYTLPAAV 17 500 KINYLLGPDA 10 268 VTQLHATDAD 9 414 N (FLLETAAY 17 533 EDKYLFTILA 10 274 TDADIGENAK 9 431 EYAIKLLAAD 17 595 TDPDYGDNSA 10 288 FSNLVSNIAR 9 809 DYVKILVAAV 17 636 QESYTFYVKA 10 296 ARRLFHLNAT 9 837 RQ_APHLKAAQ 17 648 GGRVSRSSSA 10 321 PNHKLLVLAS DLLSGTYIFA 10 691 PGTVVFCVIA 10 329 ASDGGLMPAR 9 6 GTYIFAVLLA 10 700 AVDNDTGMNA 10 331 DGGLMPARAM 14 LACVVFHSGA 10 716 VGGNTRDLFA 10 373 NIPLNTKIAL 51 LIPNKSLTTA 10 744 LGLHRVLVKA 10 382 LITVTDKDAD 9 80 DTGEIFTTGA 10 770 LFVNESVTNA 10 425 DYESTKEYAI -] ARIDREKLCA 10 783 NELVRKSTEA 10 433 AIKLLAADAG 9 104 EHCFYEVEVA 10 792 APVTPNTEIA 10 442 GKPPLN_QSAM 9 127 FLIEDINDNA 10 807 TSDYVKILVA 10 455 KVKDENDNAP 9 132 INDNAPLFPA 10 823 TVVVVIFITA 10 482 GIQLTKVSAM 9 144 INISIPENSA 10 830 ITAVVRCRQA 10 485 LTKVSAMDAD 153 AINSKYTLPA 10 835 RCRQAPHLKA 10 491 MDADSGPNAK 9 224 GGFPQRSSTA 10 846 QKNKQNSEWA 10 501 IN_YLLGPDAP 9 F25311 EIEVSIPENA 10 $$4 NFVTIEETKA 10 534 DKYLFTILAK 9 264 VGTSVTCLHA 10 927 TFKPDSPDLA 10 596 DPDYGDNSAV 9 fez SVTQLHATDA 10 933 PDLARHYKSA 10 637 ESYTFYVKAE 9 F2731 ATDADIGENA 10 938 HYKSASPQPA 10 649 GRVSRSSSAK 9 287 SFSNLVSNIA 10 965 ELPLDNTFVA 10 692 GTVVFQVIAV 9 295 IARRLFHLNA 10 LLSGTYIFAV 9 709 VDNDTGMNAE 9 320 TPNHKLLVLA 10 TYIFAVLLAC 9 717 GGNTRDLFAI 9 328 LASDGGLMPA 10 15 ACVVFHSGAQ 9 745 GLHRVLVKAN 372 ENIPLNTKIA 10 52 IPNKSLTTAM 9 771 FVNESVTNAT 9 381 ALITVTDKDA 10 81 TGEIFTTGAR 9 784 ELVR4CSTEAP 9 | FSNQFL_ETA | | R1DREKLCAG | | PVTPNTEIAD | 424 LDYESTKEYA 10 105 HCFYEVEVAI 9 811 VKILVMVAG 9 Table XXXVI-109P1D4 Table XXXVII-19P1D4 Table XXXVII-109P1D4 v. 1-A0203-10-mers v. 1-A3-10-mers v. 1-A3-10-mers Each peptide is a portion Each peptide is a portion Each peptide is a portion of SEQ ID NO : 3 ; each of SEQ ID NO : 3 ; each of SEQ ID NO : 3 ; each start position is start position is specified, start position is specified, specified, the length of the length of peptide is 10 the length of peptide is 10 peptide is 10 amino amino acids, and the end amino acids, and the end acids, and the end position for each peptide position for each peptide position for each peptide is the start position plus is the start position plus is the start position plus nine nine nine | DLNLSLIPNK | t PVi-TQSFVTV |g 824 W_WIFITAV 9 220 KVEDGGFPQR 21 504 LLGPDAPPEF 18 831 TAWRCRQAP) [9 333J) GLMPARAMVLt2 518'RTGMLTVVKKtjjS R|KNKQNSEWAT|E R|KL_MDAGKP|E | VIRPNISFDR | F88-51 FVTIEETKAD |E |QVAVDNDTG| |KVTINVVDVN| 928 FKPDSPDLAR 9 g3g (ppHLKAAQK 21 674 IVPPSNCSYE 18 934 Dl_. ARHYKSAS 9 64 KLVYKTGDVP 20 700 AVD_NDTGMNA 18 939 YKSASPQPAF 9 73 PLIRIEEDTG 20 769 NLFVNESVTN 18 fol LPLDNTFVAC 9 76 RlEEDTGEIF 20 825 VVV_IFITAVV 18 196 DKMPQLIVQK 20 864 MIMMKKKKKK 98 TabIeXXXVII-109P1D4 360 IVNPVNDTVV 20 910 DLEEQTMGKY 18 v. 1-A3-10-mers-- . H31 NNSPG ! QLTK 1E wil DLARHYKSAS 1 of SEQ ID N0 : 3 ; each 487 KVS_AMDADSG 20 42 DLLKDLNLSL 17 start position is specified, 517 CRTGMLTVVK 20 99 GIPRDEHCFY 17 the length of peptide is 10 523 TWKKtDREK 20 121 RLV_K1RFLIE 17 amino acids, and the end 0--0 position for each peptide 540 ILAYDNGVPP 20 167 DVGINGVQNY 17 is the start position plus F_ nixe 779 ATLINELVRK 20 308 LITIKEPLDR 17 743 DLGLHRVLVK 28 16 CVVFHSGAQE 19 314 PLDREETPNH 17 743] 28 407 RLRPVFSNQF 27 163 AVD_PDVG1NG 19 433 AlIfLLAADAG 17 EE L rr a5E gr'WSK1S 421 AAYLDYESTK 25 47 lLETAAYLDY 19 503 YLLGPDAPPE 17 F F4171 F503] IF SUPNKSLTT 24 == 'TDPDY TiLAKDNGVP 379 KIALITVTDK 24 617 TIDSQTGVIR 19 546 GVPPLTSNVT 17 | AV_GTITVW | EjE GV ! RPNISFD | S|NLPRHGTVGL|H E rRDz mr S er [P 206 ELDREEKDTY 23 715 1V_GGNTRDLF 19 635 KQESYTFYVK 17 m KCDVTD S J== YVKAEDGGRV 200 QLIVQKELDR 22 'KTGDVPL 8 693 TVVFQVIAVD 17 xjr 22 ELHL_ATTGLIT jR R| LVMNDLGQP |g 527 KLDREKEDKY 22 301 HLN_ATTGLIT 18 750 LVK_ANDLGQP 17 F81 YVKIL VAAVA 22 326 LVL_ASDGGLM 18 765 WIVNLFVNE 17 813 ILVAAVAGTI 22 327 VLA_SDGGLMP 18 803 VSSPTSDYVK 17 434 IKLLAADAGK 18 894 LVAAVAGTIT 17 Table XXXVII-109P1D4 Table XXXV11-109P1D4 Table XXXVII-109P1D4 v. 1-A3-10-mers v. 1-A3-10-mers v. 1-A3-10-mers Each peptide is a portion Each peptide is a portion Each peptide is a portion of SEQ ID NO : 3 ; each of SEQ ID NO : 3 ; each of SEQ ID NO : 3 ; each start position is specified, start position is specified, start position is specified, the length of peptide is 10 the length of peptide is 10 the length of peptide is 10 amino acids, and the end amino acids, and the end amino acids, and the end position for each peptide position for each peptide position for each peptide is the start position plus is the start position plus is the start position plus nixe nine nine nine |KK_KKKHSPK|S R| IPENSAINSK |S M| FL ! EDINDNA |E fez QIgPETPLNS 17 56 SKY_TLPAAVD i5 142 TVIN1SIPEN 14 Hjl NV_IGDLLKD |E m| SIPENAPVGT |g H| AINSiTLPA |E 90 RiDREKLCAG 16 267 SVTQLHATDA 15 211 EKDTYVMKVY 14 95 KLCAGIPRDE 16 276 ADIGENAKIH 15 233 AiLQVSVTDT 14 EH| EVAILPDEIF 16 315 LDREETPNHVC 15 255 EVSIPENAPV 14 EEl AILPDEIFRL 16 24 KLLVLASDGG 15 263 PVGTSVTQLH 14 E| I 96 341 VLV_NVTDVND 15 354 SIDIRYIVNP 14 241 DTNDNHPVFK |i fez NVT_DVNDNVP 15 384 TVTDKDADHN 14 291 I. VSNIARRLF 16 347 DVNDNVPSID 15 385 RVTCFTDHEI 14 340 MVLVNVTDVN 16 356 DIRYIVNPVN 15 491 MDADSGPNAK 14 363 PVN_DTVVLSE 16 369 VLSENIPLIT 15 500 KiNYLLGPDA 14 375 PLN_TKIALIT 16 370 LSENIPLNTK 15 549 PLTSNVTVFV 14 381 ALITVTDKDA 16 457 KDENDNAPVF 15 568 PVFTHNEYNF 14 416 FLLETAAYLD 16 514 SLD_CRTGMLT 15 604 AVT_LSILDEN 14 423 YLDYESTKEY 16 559 SIIDQNDNSP 15 649 GRVSRSSSAK 14 436 LLAADAGKPP 9 626 RPNISFDREK 95 710 EVRYSVVGGN 14 _kip KVKDENDNAP 16 644 KAEDGGRVSR 15 725 AIDQETGNiT 14 484 QLTKVSAMDA 16 671 PVF_IVPPSNC 15 745 GLHRVLVKAN 14 526 KKLDREKEDK 16 684 LVL_PSTNPGT 15 70 TLINELVFtKS 14 665 DVlDNKPVFI 16 761 SLFSVVIVNL 15 784 ELVRKSTEAP 14 685 VLPSTNPGTV 16 767 IVNLFVNESV 15 793 PVTPNTEIAD 14 712 RYSIVGGNTR 16 859 PEN_RQMIMMK 15 799 EIADVSSPTS 14 722 DLFAIDC, ETG 16 862 RQMIMMKKKK 15 823 TVWVIFITA 14 748 RVLVKANDLG 16 863 QMIMMKKKKK 15 834 VRCRQAPHLK 14 764 SVVVVNLFVN 16 950 IQP_ETPLNSK 15 860 ENRQMIMMKK 14 785 LVRKSTEAPV 16 961 HVIQELPLDN 15 879 KNLLLNFVl'I 14 | KlLVMMAGT | | ELPLDNTFVA |g Xl NLLLNEVTIE |i F83-3] VVRCRQAPHL 96 1004 PVSVHTRPVG 15 83 LNFVTIEETK 14 E| RV_LDLPIDL |E E| PVGIENTT |S |DVDSDGNRVT|E 909 iDLEEQTMGK 16 12 VLLACVVFHS 14 904 TLDLPlDLEE 94 990 SVSDCGYPVI"16 36 ENVLIGDLLK 14 906 DLP1DLEEQT 94 F3811 VLIGDLLKDL 15 51 LIPNI (SLTTA 4 967 PLDNTFVACD 94 43 LLKDLNLSLI 15 58 TTA_MQFKLVY 14 971 TFVACDSISK 14 55 KSLTTAMQFK 15 59 TAMQFKLVYK 14 972 FVACDSISKC 14 998 E1FRLVK1RF 15 124 KIRFLIEDIN 14 977 Sl_SKCSSSSS 14 | Table DOO (V111-109P1D4 | Tabie DOOCV111-109P1D4 v. 1-A3-10-mers v. 1-A26-10-mers v. 1-A26-10-mers Each peptide is a portion Each peptide is a portion Each peptide is a portion of SEQ ID NO : 3 ; each of SEQ ID NO : 3 ; each of SEQ ID NO : 3 ; each start position is specified, start position is specified, start position is specified, the length of peptide is 10 the length of peptide is 10 the length of peptide is 10 amino acids, and the end amino acids, and the end amino acids, and the end position for each peptide position for each peptide position for each peptide is the start position plus is the start position plus is the start position plus nine nine nine r 997 PVTTFEVPVS 14 58 TTAMQFKLVY 20 761 SLFSVVIVNL 18 19 ETPEGDKMPQ 20 833 WRCRQAPHL 8 Table t-109P1D4'213"DTYVMKVKVE 20 953 j) ETPLNSKHHi jtis) v. 1-A26-10-mers 255 EVSIPENAPV 20 33 EMPENVLIGD 17 Each peptide is a portion 347 DVNDNVPSiD 20 113 AILPDE1FRL 97 of SEQ ! D N0 : 3 ; each start position is specified, F3-6-611 DTWLSENIP 20 178 LIKSQNIFGL 17 the length of peptide is 10 494 DSGPNAKINY 20 241 DTNDNHPVFK 17 amino acids, and the end posifion for each peptide 555 TVFVSIIDQN 20 262 APVGTSVTQL 17 is the start position plus 673 FIVPPSNGSY 20 293 SNIARRLFHL 17 nine 737 EKCDVTDLGL 20 363 PVNDTVVLSE 17 776 VTNATLINEL 20 554 VTVFVSIIDQ 17 167 DVGINGVQNY 32 902 RVTLDLPIDL 20 632 DREKQESYTF 17 -- I ETPNHKLLVLI SIVGGNTRDL 111 EVAILPDEIF 28 1002 EVPVSVHTRP 20 775 SVTNATLINE 17 118 EIFRLVKIRF 27 142 TVINISIPEN 19 809 DYVKILVAAV 17 704 DTGMNAEVRY 26 251 ETEIEVSIPE 19 823 TWVVIFITA 17 188 DVIETPEGDK 25 396 DREETPNNKL 19 16 CVVFHSGAQE 96 | EVRYSIVGGN 25 623 GVIRPNISFD 19322 EEMPENVLIG 16 109 EVEVA1LPDE 24 665 DVNDNKPVFI 19 37 NVLIGDLLKD 96 350 DNVPSIDIRY 24 693 TWFQVIAVD 19 38 VLIGDLLKDL 16 367 TWLSENIPL 24 764 SVVVVNLFVN 19 117 DEfFRLVKiR 16 740 DVTDLGLHRV 24 $p2 DVSSPTSDYV 19 172 GVQNYELIKS 16 820 GTITVVVVIF 24 824 VVWIFITAV 19 210 EEKDTYVMKV 16 IDIGENAKIHF F30911 ITIKEPLDRE] 16 428 STKEYAIKLL 23 gg7 DPYSVSDCGY 19 399 FTDHEIPFRL 16 890 ETKADDVDSD 23 42 DLLKDLNLSL 18 410 PVFSNQFLLE 16 JtJ) DVPLIRIEED 22 65 LVYKTGDVPL 18 522 LTWKKLDRE 16 130 EDINDNAPLF 22 gp DTGEIFTTGA 18 529 DREKEDKYLF 16 fez EIPFRLRPVF 22 g3 EVFTTGARID 18 531 EKEDKYLFTI 16 568 PVFTHNEYNF 22 291 LVSNIARRLF 18 612 ENDDFTISQ 16 729 ETGNITLMEK 22 q. g ETAAYLDYES 18 662 NWDVNDNKP 16 910 DLEEQTMGKY 22 461 DNAPVFTQSF 18 741 VTDLGLHRVL 16 X| ELDREEKDTY | E| EYNFYVPENL |g E| LVMNDLGQP | 427 ESTKEYAIKL 21 5gg DYGDNSAVTL 18 799 EIADVSSPTS 16 601 DNSAVTLSIL 21 692 GTWFQVIAV 18 801 ADVSSPTSDY 16 | TTFKPDSPDL1 | IVGGNTRDLF li | ITWVVIFIT |g Tab) XXXVNI-109P1D4 Table XXXIX-109P1 D4 Table XXXIX-109P1D4 v. 1-A26-10-mers v. 1-B0702-10-mers v. 1-B0702-10-mers Each peptide is a portion Each peptide is a portion Each peptide is a portion of SEQ ID NO : 3 ; each of SEQ ID NO : 3 ; each of SEQ ID NO : 3 ; each start position is specified, start position is specified, start position is specified, the length of peptide is 10 the length of peptide is 10 the length of peptide is 10 amino acids, and the end amino acids, and the end amino acids, and the end position for each peptide position for each peptide position for each peptide is the start position plus is the start position plus is the start position plus nine nine nine 972 FVACDSISKG 16 547 VPPLTSNVTV 1 160 LPAAVDPDVG 13 1006 SVNTRPVGIQ 16 596 DPDYGDNSAV 18 282 AKIHFSFSNL 13 EEl PPSNCSYELV |H H| EPLDREETPN |S Table XXXIX-109P1D4 856 TPNPENRQMI 98 333 GLMPARAMVL 13 v. 1-B0702-10-mers S| QPAFQIQPET |S S| NPVNDTVVLS |D Each peptide is a portion E3t VPVSVHTRPV 18 437 LAADAGKPPL 13 of SEQ ID NO : 3 ; each start position is specified, l EEl FPATVINISI |S R| SPGIQLTKVS lM the length of peptide is 10 579 VPENLPRHCT 17 541 LAKDNGVPPL 13 amino acids, and the end position for each peptide 87 SPKNLLLNFV 17 582 NLPRHGTVGL 13 is the start position plus 72 VPLIRIEEDT 16 598 DYGDNSAVTL 13 nine 444 PPLNQSAMLF 9& 601 DNSAVTLSIL 13 H| PPEFSLDCRT 16 677 PSNCSYELVL 13 262 APVGTSVTQL 23 ILMEKCDVTDLI 3|TPEGDKMPQL|E | LPIDLEEQTM | E|LMEKCDVTDL|S 226 FPQRSSTAIL 22 954 TPLNSKHHII 16 737 EKCDVTDLGL 13 443 KPPLNQSAML 22 115 LPDEIFRLVK 15 753 ANDLGQPDSL 13 506 GPDAPPEFSL 22 936 APLFPATVIN 15 833 VVRCRQAPHL 13 52 fPNKSLTTAM 29 335 MPARAMVLVN 15 874 KKNSPKNLLl. 13 409 RFVFSNQFLL 21 532 KEDKYLFTIL 15 929 KPDSPDLARN 93 496 GPNAKfNYLL 21 g7 AVAGT1TVW 15 805 SPTSDYVKIL 21 ggg VDSDGNRVTL 15 Table F3471 MPENVL. IGDL 20 LSGTYIFAVL 14 109 1 D4 MPQLIVQKEL 0 109PID4 198 MPQLIVQKEL 20 40 IGDLLKDLNL 14 v. 1-B08- 675 VPPSNCSYEL 20 65 LVYKTGDVPL 14 10-mers F686l LPSTNPGTVV Fl 1-911 IFRLVKIRFL 14 QPDSLFSVVI 20 No 1010 RPVGIQVSNT 20 319 ETPNHKLLVL 14 Found. 352 VPSIDIRYIV 9 361 VNPVNDTVVL 14 | APVFTQSFVT |S S| IPFRLRPVFS |E I Table R| PPLTSNVTVF |S E|SDGNRVTLDL|E XLI- LPRHGTVGL I 19 947 AFQIQPETPL 14 109P1D4 NPGTVVFQVII 19 KHHIIQELPL I-ILPLDNTFVAEI I 0-mers tf SU in9 YPVTTFEVPV 1 g| DLLKDLNLSL | I 320 TPNHKLLVLA 18 100 IPRDEHCFYE 13 No ! IPLNTKIALI 1E HL AILPDEIFRL} g Found. Table XLIV-109P1D4 Table XLIV-109P1D4 v. 1-B4402-10-mers v. 1-B4402-10-mers Table Each peptide is a portion Each peptide is a portion XLII-of SEQ ID NO : 3 ; each of SEQ ID NO : 3 ; each 109P1 D4 start position is specified, start position is specified, the length of peptide is 10 the length of peptide is 10 amino acids, and the end amino acids, and the end 0-mers position for each peptide position for each peptide is the start position plus is the start position plus nine nine Nu Found. 633 REKQESITFY 20 206 ELDREEIDTY 15 round. | VEVAILPDEI |i | EEKDTYVMKV |g Tabfe 32 EEMPENVLI 18 291 LVSNIARRLF 15 XLIII-7 EEDTGEIFTT 98 293 SNIARRLFNL 15 109P1D4 130 EDINDNAPLF 1 390 ADHNGRVfCF 15 B2709- 402 HEIPFRLRPV 18 403 EIPFRLRPVF 15 10-mers 709 AEVRYSIVGG 18 407 RLRPVFSNQF F15] 0 38 VLIGDLLKDL 17 427 ESTKEYAIKL 15 No 2g2 AKIHFSFSNL 17 430 KEYAIKLLAA 15 Found. 318 EETPNHKLLV 17 582 NLPRHGTVGL 15 319 ETPNHKLLVL 17 896 VDSDGNRVTL 15 Table XLIV-109P1 D4 414 NQFLLETAAY 17 941 SASPQPAFG21 15 v. 1-B442-10-mers I 428 STKEYAIKLL 17 952 PETPLNSKHH 15 Each peptide is a portion 495 SGPNAKINYL |E m| SGTYIFAVLL |E of SEQ ID NO : 3 ; each all FHSGAQEKNY 14 start position is specified, the length of peptide is 10 117 DEIFRLVKIR 16 34 MPENVLIGDL 14 amino acids, and the end EEl EIFRLVKIRF 16 108 YEVEVAILPD 14 position for each peptide is the start position plus 252 TEIEVSIPEN 96 312 KEPLDREETP 14 I APVGT I DNVPSIDIR F 333 GLMPARAMVL 16 351 NVPSIDIRYI 14 zu REETPNHKLL 24 373 NIPLNTKIAL 16 361 VNPVNDTVVL 14 476 PENNSPGIQL 23 519 TGMLTWKKL 16 374 IPLNTKIALI 14 532 KEDKYLFTiL 23 645 AEDGGRVSRS 16 397 TCFTDHEIPF 14 992 EEQTMGKYNW 23 T53 ANDLGQPDSL 16 423 YLDYESTKEY 94 176 YELIKSQNIF 22 790 TEAPVTPNTE 16 444 PPLNQSAMLF 14 773 NESVTNATLI 22 820 GTITWVVIF 16 457 KDEfVDNAPVF 14 mu PENVLIGDLL F211 30 1 PDSPDLARHY 82 GEIFTTGARI 21 1Q01 FEVPVSVHTR 16 494 DSGPNAKINY 14 - I IEDINDNAPL I QEKNYTIREE ILLGPDAPPEFI 149 PENSAINSKY 21 A8 NLSLIPNKSL 15 511 PEFSLDCRTG 14 193 PEGDiMPQLI 21 54 NKSLTTAMQF 1 527 KLDREKEDKY 94 31 REEMPENVLI 20 119 IFRLVK (RFL 15 548 PPLTSNVTVF 14 98 AGIPRDEHCF fez 1 VKIRFLIEDI 115 GLITVTDPDY 14 113 AILPDEIFRL 20 137 PLFPATVINI 15 598 DYGDNSAVTL 14 279 GENAKIHFSF 20 190 IETPEGDKMP 15 607 LSILDENDDF 14 371 SENIPLNTKI 616 FTIDSQTGVI Table XLIV-1 9P1 D4 Table XLIV-109P1 D4 Table XLIV-109P1 D4 v. 1-B4402-10-mers v. 1-B4402-10-mers v. 1-B4402-10-mers Each peptide is a portion Each peptide is a portion Each peptide is a portion of SEQ ID NO : 3 ; each of SEQ ID NO : 3 ; each of SEQ ID NO : 3 ; each start position is specified, start position is specified, start position is specified, the length of peptide is 10 the length of peptide is 10 the length of peptide is 10 amino acids, and the end amino acids, and the end amino acids, and the end position for each peptide position for each peptide position for each peptide is the start position plus is the start position plus is the start position plus nine nine nine 687)) PSTNPGTVVF 14 531 EKEDKYLFTI 13 226 FPQRSSTAIL 12 '7141) SIVGGNTRDL 94 566 NSPVFTHNEY 13 240 TDTNDNHPVF 12 | EKCDVTDLGL IE | PVFTHNEYNF lii | KETEIEVSIP |g 7471 VTDLGLHRVL 14 573 NEYNFYVPEN 13 299 LFHL. NATTGL 12 754 NDLGQPDSLF 14 574 EYNFYVPENL 13 300 FHLNATTGL) 92 762 LFSVVIVNLF l H| DENDDFTIDS |g X| LNATTGLITI |g 776 VTNATLINEL 14 630 SFDREKQESY 13 316 DREETPNHKL 12 801 ADVSSPTSDY 14 636 QESYTFYVKA 13 367 TWLSENIPL liM 805 SPTSDYVKIL 14 673 FIVPPSNCSY 13 399 FTDNEIPFRL 12 819 AGTITWVVI 14 715 IVGGNTRDLF 13 417 LLETAAYLDY 12 845 AQKNKQNSEW 14 724 FAIDQETGNI 13 426 YESTKEYAIK 12 S|PENRQMIMMK|E EI QETGNITLME lii | LDREKEDKYL |i 872 KKKKHSPKNL tel4 747 HRVLVKANDL 13 541 LAKDNGVPPL 12 879 KNLLLNFVTI 14 798 TEIADVSSPT 13 561 IDQNDNSPVF 12 898 SDGNRVTLDL 14 804 SSPTSDYVKI 13 580 PENLPRHGTV |g 957 NSKHHiIQEL 14 873 KKKHSPKNLL 13 601 DNSAVTLS1L 12 964 QELPLDNTFV 14 8 4 KKHSPKNLLL 13 652 SRSSSAKVTI 12 992 SDCGYPVTTF 14 876 NSPKNLLLNF 13 664 VDVNDNKPVF 12 1012 VGIQVSNTTF 14 889 EETKADDVDS 13 877 PSNCSYELVL 12 MDLLSGTYIF 13 902 RVTLDLPIDL 13 690 NPGTVVFQVI 12 LSGTYIFAVL 13 939 YKSASPQPAF 13 717 GGNTRDLFAI 12 1Q FAVLLACVVF 13 947 AFQIQPETPL 13 726 IDQETGNITI. 12 40 IGDLLKDLNL 13 953 ETPLNSKHHI 13 736 MEKCDVTDLG 12 56 SLTTAMQFKL 13 963 IQELPLDNTF 13 783 NELVRKSTEA 12 87 TGARIDREKL 13 30 IREEMPNVL 12 856 TPNPENRQMI 12 105 HCFYEVEVAI 13 42 DLLKDLNLSL 12 888 IEETKADDVD 12 135 NAPLFPATVI 13 58 TTAMQFKLVY 12 911 LEEQTMGKYN 12 178 LIKSQNIFGL 13 68 KTGDVPLIRI 12 919 YNWVTTPTTF 12 198 MPQLIVQKEL 13 75 IRIEEDTGEI 12 926 TTFKPDSPDL 12 221 VEDGCFPQRS 13 77 fEEDTGEIFT 12 959 KHHIIQELPL 12 254 IEVSIPENAP 13 93 REKLCAGIPR 12 980 KCSSSSSDPY 12 NLVSNIARRL 415 QFLLETAAYL 13 111 EVAILPDEIF 12 Table 443 KPPLNQSAML 13 145 NISIPENSAI 12 1 9P1D4 F4578 DENDNAPVFT 13 151 NSAINSKYTL 12 v. 1- H| FSLDCRTGML |E R|TPEGDKMPQL|E B5101- F, o-mers Table XLVI-109PID4v. 1-DRB1 Table XLVt-109P1D4v. 1-DRB1 0101-15-mers 0101-15-mers No Each peptide is a portion of SEQ Each peptide is a portion of SEQ ID NO : 3 ; each start position is ID NO : 3 ; each start position is specified, the length of peptide is specified, the length of peptide is Found. 15 amino acids, and the end 15 amino acids, and the end position for each peptide is the position for each peptide is the Table XLVI-109P D4v. 1-DRB start position plus fourteen start position plus fourteen 0101-15-mers Each peptide is a portion of SEQ I E| GDLLKDLNLSLIPNK |B m| RYSIVGGNTRDLFAI |E 1D N0 : 3 ; each start position is 6 QFKLVYKTDVPLIR 25 745 GLNRVL. VKANDLGQP 24 specified, the length of peptide is 15 amino acids, and the end 104 EHCFYEVEVAfLPDE 5 760 DSLFSWIVNLFVNE 24 position for each peptide is the 176 YELIKSQNIFGLDVI 25 822 ITWVVIFITAWRC 24 start poiiion plus fiourteen start 6 VMKVKVEDGGFPQRS 25 85 FVTIEETKADDVDSD 24 808 SDYVKILVAAVACTI 36 223 DGGFPQRSSTAILQV 25 900 GNRVTLDLPIDLEEQ 24 TYIFAVLLACVVFHS 34 296 ARRLFHLNATTGLIT 25 919 YNWVTTPTTFKPDSP 24 265 GTSVTQLHATDADIG 34 325 LLVLASDGGLMPARA 25 975 CDSISKCSSSSSDPY 24 482 G1QLTKVSAMDADSG 33 337 ARAMVLVNVTDVNDN 25 3 LLSGTYIFAVLLACV 23 498 NAKINYLLGPDAPPE 33 433 AIKLLAADAGKPPLN 25 45 KDLNLSLIPNKSLTT 23 E| HFSFSNLVSNIARRL |M H| IKLLMDAGKPPLNQ |E m| EEDTGEIFTTGARID |E 173 VQNYELIKSQNIFGL 31 58 PENLPRHGTVGLITV 25 129 IEDINDNAPLFPATV 23 | PFRLRPVFSNQFLLE 30 63 NDDFTIDSQTGVIRP 25 151 NSAINSKYTLPAAVD 23 117 DEIFRLVKIRFLIED 2g 640 TFYVKAEDGGRVSRS 25 167 DVGINGVQNYEIIKS 23 ES| NSKYTLPAAVDPDVG 28 730 TGNITLMEKCDVTDL 25 281 NAKIHFSFSNLVSNI 23 m RRLFHLNATTGLITI 28 64 SVVIVNLFVNESVTN 25 289 SNLVSNIARRLFHLN 23 710 EVRYSIVGGNTRDLF 8 811 VKILVAAVAGTITW 25 342 LVNVTDVNDNVPSID 23 F7170 NTEiADVSSPTSDYV 28 925 PTTFKPDSPDLARHY 25 349 NDNVPSfDIRYIVNP 23 882 L. LNFVTIEETKADDV 28 936 ARHYKSASPQPAFQI 25 370 LSENIPLNTKIALIT 23 S| QPAFQIQPETPLNSK 28 2 NYTIREEMPENVLIG 24 379 KIALITVTDKDADHN 23 109 EVEVAILPDEIFfttV 27 46 DLNLSLIPNKSLTTA 24 531 EKEDKYLFTILAKDN 23 413 SNQFLLETAAYLDYE 27 4 LIRIEEDTEIFTTG 24 534 DKYLFTILAKDNGVP 23 } TSDYVKILVMVAGT |M S| PDEIFRLVKIRFLlE lE m| VPPLTSNVTVFVSII |E 90 RIDREKLCAGIPRDE 26 145 NISIPENSAINSKYT 24 630 SFDREKQESYTFYVK 23 105 HCFYEVEVAILPDEI 26 322 NHKLLVLASDGGLMP 24 648 GGRVSRSSSAKV't'IN 23 141 ATVINISIPENSAIN g 324 KLLVLASDGGLMPAR 24 663 VVDVNDNKPVFIVPP 23 187 LDVIETPEGDKMPQL 26 329 ASDGGLMPARAMVLV 24 669 NKPVFIVPPSNCSYE 23 288 FSNLVSNIARRLFHL 26 331 DGGLMPARAMVLVNV 24 679 NCSYELVLPSTNPGT 23 430 KEYAIKLLAADAGKP 26 358 RYIVNPVNDTVVLSE 24 680 CSYELVLPSTNPGTV 23 431 EYAIKLLAADAGKPP 26 472 TVSIPENNSPGIQLT 24 72 INELVRKSTEAPVTP 23 538 FTILAKDNGVPPLTS 26 47 NNSPGIQLTKVSAMD 24 812 KILVAAVAGTITVVV 23 F5-7-2] HNEYNFYVPENLPFH 26 488 VSAMDADSGPNAKIN 24 819 AGTITVVVVIFITAV 23 596 DPDYGDNSAVTLSIL 26 499 AKINYLLGPDAPPEF 24 821 TITWVVIFITAVVR 23 E| KCDVTDLGLHRVLVK |E El HGTVGLITVTDPDYG |E S| VVWIFITAVVRCRQ |E 823 TVVVVIFITAWRCR 26 660 TINVVDVNDNKPVFI 24 844 AAQKNKQNSEWATPN 23 ''VPPSNCSYq m MGKYNWVTTPTTFKP 23 | EMPENVLIGDLLKDL |g | VIAVDNDTGMNAEVR | 1 IQELPLDNTFVACDS lE Table XLVI-109P1 D4v. 1-DRB1 Table XLVI-109P1 D4v. 1-DRB1 Table XLVI-109P1 D4v. 1-DRB1 0101-15-mers 0101-15-mers 0101-15-mers Each peptide is a portion of SEQ Each peptide is a portion of SEQ Each peptide is a portion of SEQ ID NO : 3 ; each start position is D NO : 3 ; each start position is ID NO : 3 ; each start position is specified, the length of peptide is specified, the length of peptide is specified, the length of peptide is 15 amino acids, and the end 15 amino acids, and the end 15 amino acids, and the end position for each peptide is the position for each peptide is the position for each peptide is the start position plus fourteen start position plus fourteen start position plus fourteen | GTYIFAVLLACWFH | | HKLLVLASDGGLMPA | | ETPNHKLLVLASDGG | 126 RFLIEDINDNAPLFP 22 346'fDVNDNVPSIDIRYI 20 411 VFSNQFLLETAAYLD 18 Sil F221 F4251 19 F42311 YLDYESTKEYAIKLL -l LIKSQNIFGL JENDNAPVFT I AMLFIKV 251 ETEIEVSIPENAPVG 22 463 APVFTQSFVTVSIPE 20 641 FYVKAEDGGRVSRSS 1 328 LASDGGLMPARAMVL} E H| FVTVSIPENNSPGIQ |E ElGGNTRDLFAIDQETG |g F4472 HEiPFRLRPVFSNQF 22 522 LTWKKLDREKEDlY 20 750 LVKANDLGQPDSLFS 18 442 GKPPLNQSAMLFIKV 22 619 DSQTGVIRPNISFDR 20 762 LFSVVIVNLFVNESV 18 462 NAPVFTQSFVTVSIP 22 76 VNLFVNESVTNATLI 20 765 WIVNLFVNESVTNA 18 485 LTKVSAMDADSGPNA 22 783 NELVRKSTEAPVTPN 20 778 NATLINELVRKSTEA 18 -- LNFVTIEETKADDVD F779] 1 ATLINELVRKSTEAP 590 PPEFSLDCRTGMLTV 22 944 PQPAFQIQPETPLNS 20 870 KKKKKKHSPKNLLLN 18 535 KYLFTILAKDNGVPP 22 992 SDCGYPVTTFEVPVS 20 918 KYNWVTTPTTFKPDS 18 544 DNGVPPLTSNVTVFV 22 63 FKLVYKTGDVPLIRI 19 986 SDPYSVSDCGYPVTT 18 m| F 9 F9973 DCGYPVTTFEVPVSV 118 615 DFTIDSQTGVIRPNI 22 122 LVKIRFLIEDINDNA 99 995 GYPVTTFEVPVSVHT 18 683 ELVLPSTNPGTVVFQ 22 182 QNIFGLDVIETPEGD 19 '692lut GTVVFQVIAVDNDTG F221 306 TGLITIKEPLDREET 19 Table XLVII-109P1D4v. 1- 753 ANDLGQPDSLFSVVI 22 352 VPSIDIRYIVNPVND 19 DRBI 0301-15-mers 756 LGQPDSLFSVVIVNL 22 365 NDTVVLSENIPLNTK 19 Each pepfide is acportion of SEQ ID N0 ; 3 ; each start 759 PDSLFSVVIVNLFVN 22 420 TA, 4YLDYESTKEYAI 19 position is specified, the length 800 IADVSSPTSDYVK (L 22 500 KINYLLGPDAPPEFS 19 of peptide is 15 amino acids, F8175 F604] 1 AVTLSILD 815 VAAVAGTITVWVIF 22 peptide is the start position plus 939 YKSASPQPAFQIQPE 22 696 FQVIAVDNDTGMNAE 19 fourteen 947 AFQIQPETPLNSKHH 22 733 ITLMEKCDVTDLGLH 19 1001 FEVPVSVHTRPVGIQ 2 YIFAVLLACVVFHSG 18 40 IGDLLKDLNLSLIPN 38 60 AMQFKLVYKTGDVPL 21 14 LACVVFHSGAQEKNY 18 111 EVAILPDEIFRLVKI 32 108 YEVEVAILPDEIFRL 29 40 IGDLLKDLNLSLIPN 18 900 GNRV'TLDLPIDLEEQ 31 E31 IFGLDVIETPEGDKM | | SLIPNKSLTTAMQFK |g | ENVLIGDLLKDLNLS} 363 PVNDTVVLSENIPLN 21 54 NKSLTTAMQFKLVYK 18 74 LIRIEEDTGEIFTTG 29 GVPP TGEIFTTG 18 CAGIPRDEHCFYEVE 2n9 722 DLFAIDQETGNITLM 21 133 NDNAPLFPATVINIS 18 125 IRFLIEDINDNAPLF 29 143 VINISIPENSAINSK 20 936 APLFPATVINISIPE 18 502 NYLLGPDAPPEFSLD 29 215 YVMKVKVEDGGFPQR 20 170 INGVQNYELIKSQNI 98 893 ADDVDSDGNRVTLDL 28 222 EDGGFPQRSSTAILQ 20 245 NHPVFKETEIEVSlP 18 365 1JDTVVLSENIPLN1'K 27 246 HPVFKETEIEVSIPE 20 257 SIPENAPVGTSVTQL 18 605 VTLSILDENDDFTID 27 253 EIEVSIPENAPVGTS 20 293 SNIARRLFHLNATTG 18 671 PVFIVPPSNCSYELV 27 Table XLVII-109P1D4v. 1- Table XLVII-109P1D4v. 1- Table XLVIII-109P1D4v. 1- DRBI 0301-15-mers DRBI 0301-15-mers DRB1 0401-15-mers Each peptide is a portion of Each peptide is a portion of Each peptide is a portion of SEQ SEQ ID NO : 3 ; each start SEQ ID NO : 3 ; each start ! D NO : 3 ; each start position is position is specified, the length position is specified, the length specified, the length of peptide is of peptide is 15 amino acids, of peptide is 15 amino acids, 15 amino acids, and the end and the end position for each and the end position for each position for each peptide is the peptide is the start position plus peptide is the start position plus start position plus fourteen fourteen fourteen l l| m| VQNYELIKSQNIFGL |B 904 TLDLPIDLEEQTMGKK 27 288 1 FSNLVSNIARRLFH 20 281 46 DLNLSUPNKSLTTA j (26 413) SNQFLLETAAYLDYE (20'5101 PPEFSLDCRTGMLTV f28 i| NKSLT 26 434 IKLLAADAGKPPLNQ 20 613 NDDFTIDSQTGVIRP 28 3F7111 SENIPLNTKIALITV 26 580 PENLPRHGTVGLITV 20 916 MGKYNWVTTPTTFKP 28 525 VKKLDREKEDKYLFT 26 696 FQVIAVDNDTGMNAE 20 40 IGDLLKDLNLSLIPN 26 613 NDDFTIDSQTGVIRP 26 803 VSSPTSDYVKILVAA 20 46 DLNLSLIPNKSLTTA 26 626 RPNISFDREKQESYT 26 861 NRQMIMMKKKKKKKK 20 54 NKSLTTAMQFKLVYK 26 204 QKELDREEKDTYVMK 25 908 PIDLEEQTMGKYNWV 20 125 IRFLIEDINDNAPLF 26 2F7511 DADIGENAKIHFSFS 25 928 FKPDSPDLARHYKSA 20 167 DVGINGVQNYELIKS 26 289 SNLVSNIARRLFHLN 25 904 EHCFYEVEVAILPDE 19 354 SfDIRYIVNPVNDTV 26 401 DHEIPFRLRPVFSNQ 25 109 EVEVAILPDEiFRLV 19 544 DNGVPPLTSNVTVFV 26 510 PPEFSLDCRTGMLTV 25 117 DEIFRLVKIRFLIED 19 555 TVFVSIIDQNDNSPV 26 i| NSPVFTHNEYNFYVP 25 182 QNIFGLDVIETPEGD 19 704 DTGMNAEVRYSIVGG 26 F6-62] NWDVNDNKPVFNP 25 186 GLDVIETPEGDKMPQ 19 76 VVIVNLFVNESVTNA 26 713 YSIVGGNTRDLFAID 25 l9Q IETPEGDKMPQLIVQ 19177g ATLINELVRKSTEAP 26 EN| PDEIFRLVKIRFLIE 24 198 MPQLIVQKELDREEK 19 7g7 NTEIADVSSPTSDYV 26 Ml DVGINGVQNYEL1KS 24 238 SVTDTNDNHPVFKET 19 823 TVVVVIFITAWRCR 26 395 RVTCFTDHEIPFRLR 24 305 TTGLITIKEPLDREE 19 827 VIFITAVVRCRQAPH 26 F7-211 RDLFA1DQETGN1TL 24 331 DGGLMPARAMVLVNV 19 gg3 ADDVDSDGNRVTLDL 26 325 LLVLASDGGLMPARA 23 415 QFLLETAAYLDYEST 19 963 IQELPLDNTFVACDS 26 F6-28 NISFDREKQESYTFY 23 421 AAYLDYESTKEYAIK 19 7 TyFAVLLACVVFHS 22 945)) QPAFQIQPETPLNSK 23 452 LFIKVKDENDNAPVF 19 16 CVVFHSGAQEKNYTI 22 161 PAAVDPDVGiNGVQN 22 518 RTGMLTWKKLDREK 19 104 EHCFYEVEVAILPDE 22 | VSAMDADSGPNAKIN 22 519 TGMLTWKKLDREKE 19 117 DEIFRLVKIRFLIED 22 925 PTTFKPDSPDLARHY 22 567 SPVFTHNEYNFYVPE 19 124 KIRFLIEDINDNAPL 22 F97-O] NTFVACDSISKCSSS lg | TVGLITVTDPDYGDN |g | RRLFHLNATTGLITI |g H| DPDVGINGVQNYELI 21 682 YELVLPSTNPGTVVF 19 413 SNQFLLETAAYLDYE 22 323 HKLLVLASDGGLMPA 21 712 RYSIVGGNTRDLFAI 19 467 TQSFVTVSIPENNSP 22 405 PFRLRPVFSNQFLLE 21 730 TGNITLMEKCDVTDL 19 gg NfSFDREKQESYTFY 22 F53-8] FTILAKDNGVPPLTS 21 746 LHRVLVKANDLGQPD 19 670 KPVFIVPPSNCSYEL 22 698 VIAVDNDTGMNAEVR 21 791 EAPVTPNTEIADVSS 19 679 NCSYELVLPSTNPGT 22 759 PDSLFSVVIVNLFVN 21 831 TAWRCRQAPHLKAA l9 721 RDLFAIDQETGNITL 22 963 IQELPLDNTFVACDS 21 839 APHLKAAQKNKQNSE 19 768 VNLFVNESVTNATLI 22 | FKLVYKTGDVPLIRI | S|RQMIMMKKKKKKKKH1S | TSDYVKILVAAVAGT |g 128 L1ED1NDNAPLFPAT 20 864 M1MMKKKKKKKKHSP 19 gg2 LLNFVTIEETKADDV 22 E| YELIKSQNIFGLDVI 20 g1g KYNWVTTPTTFKPDS 22 Table XLVIIi-109P1D4v. 1- Table XLVIII-109P1D4v. 1- Table XLVIII-109P1D4v. 1- DRB1 0401-15-mers DRB1 0401-15-mers DRB1 0401-15-mers Each peptide is a portion of SEQ Each peptide is a portion of SEQ Each peptide is a portion of SEQ ID NO : 3 ; each start position is ID NO : 3 ; each start position is ID NO : 3 ; each start position is specified, the length of peptide is specified, the length of peptide is specified, the length of peptide is 15 amino acids, and the end 15 amino acids, and the end 15 amino acids, and the end position for each peptide is the position for each peptide is the position for each peptide is the start position plus fourteen start position plus fourteen start position plus fourteen E| PTTFKPDSPDLARHY |E S| NDTVVLSENIPLNTK |E m| IVNLFVNESVTMATL |E 936 ARHYKSASPQPAFQI 22 366 DTVVLSENIPLNTKI 20 769 NLFVNESVTNATLIN 20 S| DNTFVACDSISKGSS 22 37 NTKIALITVTD4CDAD 20 77 NATLINELVRKSTEP, 20 998 VTTFEVPVSVHTRPV 22 379 KIALITVTDKDADHN 20 800 IADVSSPTSDYV4IL 20 6 GTYIFAVLLACWFH 20 393 NGRVTCFTDHEIPFR 20 808 SDYVKILVAAVAGTI 20 27 NYTIREEMPENVLIG 20 405 PFRLRPVFSNQFLLE 20 810 YVKILVAAVAGTITV 20 36 ENVLIGDLLKDLNLS 20 421 AAYLDYESTKEYAIK 20 811 VKILVAAVAGTITVV 20 fez NVLIGDLLKDLNLSL 20 472 TVSIPENNSPGiQLT 20 812 KILVAAVAGTITWV 20 41 GDLLKDLNLSLIPNK 20 482 GIQLTKVSAMDADSG 20 815 VAAVAGTITVWVIF 20 '48 NLSLIPNKSLTTAMQ 20 488 VSAMDADSGPNAKIN 20 819 AGTITWVVIFITAV 20 CAGIPRDEHCFYEVE I NAKINYLLGPDAPP F eue31 EVAILPDEIFRLVKI 20 522 LTVVKKLDREKEDKY 20 822 ITV1/VVIFITAVVRC 20 112 VAILPDEIFRLVKIR 20 534 DKYLFTILAKDNGVP 20 839 APHLKAAQKNKQNSE 20 122 LVKIRFLIEDINDNA 20 547 VPPLTSNVTVFVSII 20 879 r KNLLLNFVTIEETKA 20 135 NAPLFPATVINISIP 20 551 TSNVTVFVSIIDQND 20 80 NLLLNFVTIEETKAD 20 140 PATVINISiPENSAI 20 558 VSIIDQNDNSPVFTH 20 883 LNFVTIEETKADDVD 20 F14731 VINISIPENSAINSK 20 580 PENLPRHGTVGLITV 20 900 GNRVTLDLPIDLEEQ 20 157 KYTLPAAVDPDVGIN 20 606 TLSILDENDDFTIDS 20 904 TLDLPIDLEEQTMGK 20 eue| SQNIFGLDVIETPEG 20 640 TFYVKAEDGGRVSRS 20 906 DLPIDLEEQTMGKYN 20 184 IFGLDVIETPEGDKM 20 648 GGRVSRSSSAKVTIN 20 947 AFQIQPETPLNSKHH 20 231 STAILQVSVTDTNDN 20 658 KVTINVVDVNDNKPV 20 959 KHHIIQELPLDNTFV 20 232 TAILQVSVTDTNDNH 20 661 INVVDVNDNKPVFIV 20 960 HHIIQELPLDNTFVA 20 234 ILQVSVTDTNDNHPV 20 682 YELVLPSTNPGTVVF 20 975 CDSISKCSSSSSDPY 20 F24751 NHPVFKETEIEVSIP 20 692 GTWFQVIAVDNDTG 20 995 GYPVTTFEVPVSVHT 20 253 EIEVSIPENAPVGTS 20 695 VFQVIAVDNDTGMNA 20 12 VLLACVVFHSGAQEK 18 265 GTSVTQLHATDADIG 20 696 FQVIAVDNDTGMNAE 20 13 LLACVVFHSGAQEKN 18 281 I VIAVDNDTGMNAEVR IF FHSGAQEKNYTIREE Im 289 SNLVSNIARRLFHLN 20 712 RYSIVGGNTRDLFAI 20 51 LIPNKSLTTAMQFKL 18 312 KEPLDREETPNHKLL 20 720 TRDLFAIDQETGNIT 20 73 PLIRIEEDTGEIFTT 18 322 NHKLLVLASDGGLMP 20 723 LFAIDQETGNITLME 20 78 EEDTGEIFTTGARID 18 323 HKLLVLASDGGLMPA 20 738 KCDVTDLGLHRVLVK 20 85 FTTGARIDREKLCAG 18 331 DGGLMPARAMVLVNV 20 743 DLGLHRVLV4 (ANDLG 20 113 AILPDEIFRLVKIRF 18 837 ARAMVLVNVTDVNDN 20 747 HRVLVKANDLGQPDS 20 137 PLFPATVINISIPEN 18 338 RAMVLVNVTDVNDNV 20 753 ANDLGQPDSLFSVVI 20 144 INISIPENSAINSKY 18 S| NDNVPSIDIRYIVNP 20 759 PDSLFSVVIVNLFVN 20 148 IPENSAINSKYTLPA 18 F357] IRYIVNPVNDTWLS 20 762 LFSWIVNLFVNESV 20 96 DKMPQLIVQKELDRE 18 X| RYIVNPVNDTWLSE se 764 SVVIVNLFVNESVTN 20 201 LIVQKELDREEKDTY 18 Table XLVIII-109P1 D4v. 1- Table XLVIII-109P1D4v. 1- Table XLVIII-109P1D4v. 1- DRB1 0401-15-mers DRB1 0401-15-mers DRB1 0401-15-mers t eI. 1 Each peptide is a portion of SEQ Each peptide is a portion of SEQ Each peptide is a portion of SEQ ID NO : 3 ; each start position is D NO : 3 ; each start position is D NO : 3 ; each start position is specified, the length of peptide is specified, the length of peptide is specified, the length of peptide is 15 amino acids, and the end 15 amino acids, and the end 15 amino acids, and the end position for each peptide is the position for each peptide is the position for each peptide is the start position plus fourteen start position plus fourteen start position plus fourteen E| KVEDGGFPQRSSTAI |E m| SVTNATLINELVRKS |S E| TWFQVIAVDNDTGM |S E| QRSSTAILQVSVTDT |S E| PNTEIADVSSPTSDY |h m| EVRYSIVGGNTRDLF |R 2581 IPENAPVGTSVTQLN 18 813 ILVAAVACTITVWV 1 760 DSLFSWIVNLFVNE 16 F2672 APVGTSVTQLHATDA i E|WRCRQAPHLKMQK|S | WIFITAVVRCRQAP lg zu AKIHFSFSNLVSNIA 18 838IQAPHLKAAQKNKQNS 18 945 QPAFQIQPETPLNSK 16 F2973 SNIARRLFHLNATTG |g E|WATPNPENRQMIMMK|B | NSAINSKYTLPMVD |g 298 RLFHLNATTGLITIK 18 876 HSPKNLLLNFVTIEE 18 953 ETPLNSKHHIIQELP 15 309)) ITIKEPLDREETPNH |S M|ETKADDVDSDGNRVT|E ml MDLLSGTYIFAVLLA |E 341)) VLVNVTDVNDNVPSI 18 907 LPIDLEEQTMGKYNW 18 IFAVLLACVVFHSGA 14 F3476 TDVNDNVPSIDIRYI 18 929 KPDSPDLARHYKSAS 18 10 FAVLLACVVFHSGAQ 14 3F5011 DNVPSIDIRYIVNPV 18 930 PDSPDLARHYKSASP 18 11 AVLLACWFHSGAQE 14 F3673 PVNDTVVLSENIPLN 18 962 IIQELPLDNTFVACD 18 15 ACVVFHSGAQEKNYT 14 3F7011 LSENIPLNTKIALIT 18 992 SDCGYPVTTFEVPVS 18 44 LKDLNLSLIPNKSLT 14 385 VTDKDADHNGRVTCF 18 1001 FEVPVSVHTRPVGIQ 18 63 FKLVYKTGDVPLIRI 14 406 FRLRPVFSNQFLLET 18 223 DGGFPQRSSTAILQV 17 69 TGDVPLIRIEEDTGE 14 440 DAGKPPLNQSAMLFI 18 5 SGTYIFAVLLACVVF 16 71 DVPLIRIEEDTGEIF 14 452 LFIKVKDENDNAPVF 18 60 AMQFKLVYKTGDVPL 16 72 VPLIRIEEDTGEIFT 14 460 NDNAPVFTQSFVTVS 18 64 KLVYKTGDVPLlRIE 16 74 LIRIEEDTGEIFTTG 14 F46-411 PVFTQSFVTVSIPEN 18 82 GEIFTTGARIDREKL l6 88 GARIDREKLCAGIPR 14 F48-711 KVSAMDADSGPNAKI 18 105 HCFYEVEVAILPDEI 16 107 FYEVEVAILPDEIFR 14 E31 EKEDKYLFTILAKDN 1 136 APLFPATVINISIPE 16 109 EVEVAILPDEIFRLV 14 556 VFVSIIDQNDNSPVF 18 182 QNIFGLDVIETPEGD 16 116 PDEIFRLVKIRFLIE 14 568 PVFTHNEYNFYVPEN 18 246 HPVFKETEIEVSIPE 16 119 IFRLVKIRFLIEDIN 14 577)) FYVPENLPRHGTVGL 18 283 KIHFSFSNLVSNIAR 16 26 RFLIEDINDNAPLFP 14 ITDPDYGDNS ATVINISIPENSAIN 114 1598)) DYGDNSAVTLSILDE 18 409 RPVFSNQFLLETAAY 16 145 NISIPENSAINSKYT 14 EEl ILDENDDFTIDSQT 18 420 TAAYLDYESTKEYAI 16 161 PAAVDPDVGINGVQN 14 618 IDSQTGVIRPNISFD 18 423 YLDYESTKEYAIKLL 16 170 INGVQNYELIKSQNI 14 625 IRPNISFDREKQESY 18 450 AMLFIKVKDENDNAP 16 175 NYELIKSQNIFGLDV 14 645 AEDGGRVSRSSSAKV 18 463 APVFTQSFVTVSIPE 16 176 YELIKSQNIFGLDVI 14 ) VTINVVDVNDNKPVF 18 535 KYLFTILAKDNGVPP 16 186 GLDVIETPEGDKMPQ 14 689 TNPGTVVFQVIAVDN 18 554 VTVFVS11DQNDNSP 16 17 LDVIETPEGDftMPQL 14 740 DVTDLGLHRVLVKAN 18 572 HNEYNFYVPENLPRH 16 195 GDKMPQLIVQKELDR 14 750 LVKANDLGQPDSLFS 18 574 EYNFYVPENLPRHGT 16 200 QLIVQKELDREEKDT 14 756 LGQPDSLFSVVIVNL 18 575 YNFYVPENLPRHGTV 16 2Q4 QKELDREEKDTYVMK 14 T) SLFSVVIVNLFVNES 18 596 DPDYGDNSAVTLSIL 16 213 DTYVMKVKVEDGGFP 14 E| LFVNESVTNATLINE 18 639 YTFYVKAEDGGRVSR 16 216 VMKVKVEDGGFPQRS 14 Table XLVI II-109P1 D4v. 1- Table XLVII I-109P1 D4v. 1- Table XLIX-109P1 D4v. 1-DRB1 DRB1 0401-15-mers DRB1 0401-15-mers l 1101-15-mers Each peptide is a portion of SEQ Each peptide is a portion of SEQ Each peptide is a portion of SEQ ID NO : 3 ; each start position is ID NO : 3 ; each start position is ID NO : 3 ; each start position is specified, the length of peptide is specified, the length of peptide is specified, the length of peptide is 15 amino acids, and the end 15 amino acids, and the end 15 amino acids, and the end position for each peptide is the position for each peptide is the position for each peptide is the start position plus fourteen start position plus fourteen start position pius fourteen - 1 25 ETEIEVSIPENAPVC 94 622 TGl/IlPNISFDREI4Q 14 16 PDEIFFLVKIRFLIE 5 '255' EVSIPENAPVGTSVT 14 626 RPNISFDREKQESYT 14 285 HFSFSNLVSNIARRL 25 261 NAPVGTSVTQLHATD 14 656 SAKVTINVVDVNDNK 14 1000 TFEVPVSVHTRPVGI 25 1FSNLV--IIAMQFKLVYKTGDVPLI 24 296 ARRLFHLNATTGLIT 14 663 VVDVNDNKPVFIVPP 14 58 RTGMLTWKKLDREK 23 299 LFHLNATTGLITIKE 14 669 NKPVFIVPPSNCSYE 14 519 TGMLTWKKLDREKE 23 fez TTGLITIKEPLDREE 14 671 PVFIVPPSNCSYELV 14 82 LLNFVTIEETKADDV 23 F3274 KLLVLASDGGLMPAR 14 681 SYELVLPSTNPGTW 14 289 SNLVSNIARRLFHLN 22 325 LLVLASDGGLMPARA 14 683 ELVLPSTNPGTVVFQ 14 636 QESYTFYVKAEDGGR 22 339 AMVLVNVTDVNDNVP 14 708 NAEVRYSIVGGNTRD 94 730 TGNITLMEKCDVTDL 22 340 MVLVNVTDVNDNVPS 14 713 YSIVGGNTRDLFAID 14 779 ATLINELVRKSTEAP 22 342 LVNVTDVNDNVPSID 14 730 TGNITLMEKCDVTDL 14 1002 EVPVSVHTRPVGiQV 22 367 TVVLSENIPLNTKIA 14 733 ITLMEKCDVTDLGLH 14 12 VLI.. ACVVFHSGAQEK 21 371 SENIPLNTKIALITV 14 741 1/TDLGLHRVLVKAND 14 37 NVLIGDLLKDLNLSL 21 415. QFLLETAAYLDYEST 14. 773 NESVTNATLINELVR 14 342 LVNVTDVNDNVPSID 21 431 EYAIKLLAADAGKPP 14 783 NELVRKSTEAPVTPN 14 522 LTVVKKLDREKEDKY 21 AADAGKPPLN 14 VVVVIFITAVVRCRQ F8081 434 IKLLAADAGKPPLNQ 14 830 ITAWRCRQAPNLKA 14 861 NRQMIMMKKKKKKKK 21 443 KPPLNQSAMLFIKVK 14 861 NRQMIMMKKKKKKKK 14 11 AVLLACVVFHSGAQE 20 F4478 QSAMLFIKVKDENDN 14 885 FVTIEETKADDVDSD 14 82 GEIFTTGARIDREKL 20 453 FIKVKDENDNAPVFT 14 913 EQTMGKYNWVTTPTT 14 105 HCFYEVEVAILPDEI 20 462 NAPVFTQSFVi'VSIP 14 919 YNWVTTPTTFKPDSP 14 212 KDTYVMKVKVEDGGF 20 468 QSFVTVSIPENNSPG 14 932 SPDLARHYKSASPQP 14 265 GTSVTQLHATDADIG 20 F4770 FVTVS1PENNSPGIQ 14 970 NTFVACDSISKCSSS 14 293 SNIARRLFHLNATTG 20 R| F479] 1 NSPGIQLTKVSAMDA] 20 4870 NYLLGPDAPPEFSLD 14 1000 TFEVPVSVHTRPVGI 14 482 GIQLTKVSAMDADSG 20 518 RTGMLTVVKKLDREK 14 1002 EVPVSVHTRPVGIQV 14 645 AEDGGRVSRSSSAKV 20 519 TGMLTWKKLDREKE 14 932 SPDLARHYKSASPQP 20 525 VKKLDREKEDKYLFT 14 Table XLIX-109P1D4v. 1-DRB1 972 FVACDSISKCSSSSS 20 538 FTILAKDNGVPPLTS 14 1901-15-mers 136 APLFPATVINISIPE 99 Each peptide is a portion of SEQ Wt tFGLDVtETPEGDKM tl9 1D NO : 3 ; each start position is 586 HGTVGLITVTDPDYG 14 specified, the length of peptide is 15 amino acids, and the end 322 NHKLLVLASDGGLMP 19 position for each peptide is the 591 LITVTDPDYGDNSAV 14 sa position plus fiourteen 463 APVFTQSFVTVSIPE 19 60721 NSAVTLSILDENDDF 14 660 TINVVDVNDNKPVFI 19 604 AVTLSILDENDDFTI 14 535 KYLFTILA4fDNGVPP 32 2o TRDLFAIDQETGNIT 19 m| LSILDENDDFTIDSQ 14 827 VIFITAVVRCRQAPH 26 82 TITVWVIFITAVVR 19 Table XLIX-109P1D4v. 1-DRB1 Table XL1X-109P1D4v. 1-DRB1 Each peptide is a 1101-15-mers 1101-15-mers portion of SEQ ID Each peptide is a portion of SEQ Each peptide is a portion of SEQ NO : 5 ; each start 1 1D NO : 3 ; each start position is ID NO : 3 ; each start position is position is specified, specified, the length of peptide is specified, the length of peptide is the length of peptide 15 amino acids, and the end 15 amino acids, and the end is 9 amlno acids, position for each peptide is the position for each peptide is the and the end position start position plus fourteen start position plus fourteen. the start position plus weight plus eight 231 TYIFAVLLACWFHS |S S| IDSQTGVIRPNISFD |S F679 11 NCSYELVLPSTN PGT 126 RFLIEDINDN, PLFP 18 689 TNPGTVVFQVIAVDN 16 8 PTDSRTSTi 13 ES| NSKYTLPMVDPDVG |g E|DTGMNAEVRYSIVGG|S S| DSRTS-1E} 182 QNIFGLDVIETPEGD 18 710 EVRYSIVGGNTRDLF 16 NTRPTDSRT 90 r E1 DTYVMKVKVEDGGFF M, 738 KCDVTDLGLHRVLVK 16 379 KIALITVTDKDADHN 18 768 VNLFVNESVTNATLI 16 Table 431 EYAIKLLAADAGKPP 18 807 TSDYVKILVAAVAGT 16 485 LTKVSAMDADSGPNA 18 916 MGKYNWVTTPTTFKP 16 JARHYKSASPQPAFQI Terminal F4978 PPEFSLDCRTGMLTV |E A0203-9- mers 586 HGTVGLITVTDPDYG 18 Table XXII-109P1D4 '§'2 c'Termirlal-A1'', l H|VFQVIAVDNDTGMNAS 9-mers 11 T1 760 DSLFSVVIVNLFVNE 18 Results F76-411 SVViVNLFVNESVTN 18 Each pep6de s a 0 portion of SEQ ID Found. 797 NTEIADVSSPTSDYV 18 NO : 5 ; each start position is specified, TabieXXV-109P1 D4 993 DCGYPVTTFEVPVSV 9 the length of peptide v. 2 C'Terminal-A3 104 EHCFYEVEVAILPDE 17 is 9 amino acids, 9-mers and the end position Each peptide is a for each peptide in 210 EEKDTYVMKVKVEDG 17 the start position portion of SEQ ID 246 HPVFKETEIEVSIPE 17 plus eight N0 ; 5 ; each start I 1t"11 poslbon ls specfied, 11 380 IALITVTDKDADHNG 17 he length of peptide 449 SAMLFfKVffDENDNA 17 8 PTDSRTSTI 16 is 9 amino acids, and 638 SYTFYVKAEDGGRVS 17 5 NTRPTDSRT 10 the end position for 0 0 teach peptide is the 670 KPVFIVPPSNCSYEL 17 12 RTSTIEICS 10 start position plus M|TWFQVIAVDNDTGMW DSRTST ! EI IjX eight ll 744 LGLHRVLVKANDLGQ 17 14 STIEICSEI 8 L W AGTITVVVVIF1TAV ß SV_TRPTDSl 925 PTTFKPDSPDLARNY 17 TabieXXlll 1 PVSVHTRPT 10 C-Terai201 j3|SDPYSVSDCGYPVTTt C Terminal-A0201 f j38 LFPATVINISIPENS 16 g-merS 5 HTRPTDSRT 9 173 VQNYELIKSQNIFGL 16 7 RPTDSRTST 9 S| FTDHE1PFRLRPVFS} j PTDSRTST1 450 AMLFI14VKDENDNAP 16 14 STlEIGSEI 8 467 TQSFVTVSIPENNSP 16 iE31 KINYLLGPDAPPEFS t TableEVI-109P1D4|| v, 2 C'Terminal-A26 ils| VTVFVSIIDQNDNSP 16 9-mers Each peptide is a Table XXVIII Each peptide is a portion of SEQ ID 1 O9P1D4v. 2 portion of SEQ ID NO : 5 ; each start C'Terminal-BO8 NO : 5 ; each start position is specified, 9-mers position is specified, the length of peptide Each peptide is a 1l the length of peptide is 9 amino aclds, portion of SEQ ID I is 9 amino acids, and and the end position NO. 5, each start 0 the end position for for each peptide is ech peptide i ihe position i spied, P-is9aminoacids,-s'- is 9 amino acids, is 9 amino acids, and the end position Sj STIEICSEI | foreachpeptideis l | RTSTlEIC| m.. the start position 131 1plus eight 4J VHTRPTDSR) l2 F8] PTDSRTSTf T1 6 TRPTDSRTS 92 F8] RTSTIE1CS | SIPTDSRTSTIS i| ST1E1CSEI |g 1 PVSVH'FRPT 10 10 DSRTSTIEI 13 10 DSRTSTIEi 9 SjHTRPTDSRT|g i| ST1E1CSE1 IE mlRPTDSRTSTt 'f0 DSRrSI (Ef 9 3 SVHTRPTDS 10 8 PTDSRTSTI $ i|i-iTRPTDSRT| Tab (eXXVIi Table XXXI 109P1D4v. 2. I 109P1D4v. 2 C'Terminal-B0702 109PID4v. 2 C'Terminal-B2709 9-mers C'Terminal-Bl5lO-9-merFs- Each peptide is a 9-mers Each peptide is a portion of SEQ ID portion of SEQ ID NO : 5 ; each start N0 : 5 ; each start position is specified, portion of SEQ ID position is specified, the Length of peptide N0 : 5 ; each start the length of peptide is 9 amino acids, position is is 9 amino acids, and the end position specified, the and the end position for each peptide is length of peptide is for each peptide is the start position 9 amino acids, and the start position plus eight the end position for plus eight each peptide is the start position plus 11 Each peptide is a | 7 RPTDSR'fST 19 eight portion of SEQ ID N0 : 5 ; each start 1 tVSVHTRPT {10 position is specified, F5]) HTRPTDSRT the length of peptide 10 pSRTSTIEI 9 1 PVSVHTRPT 4 is 9 amino acids, and the end position 5 HTRPTDSRT) for each peptide is Table XXV) I) HITRPTDSRTS E, the start position 109P1D4v. 2 plus eight C'Terminal-BO8 Table II 9-mers t1 11 Table VO (X 11 109Pl D4v. 2 Each peptide is a C'Terminal-B2705 portion of SEQ ID 9-mers 9-mers NO : 5 ; each start 8 PTDSRTSTI 9 posifion is specified, 10 DSRTST (E ( 8 the length of peptide is 9 amino acids, and the end position Tabfe XXXft for each peptide is 109P1 D4v. 2 the start position C'Terminal-B4402 plus eight 9-mers II L 11 Each peptide is a Table XXXV Table XXXVIII portion of SEQ ID 109P1D4v. 2 109P1D4v. 2 C' NO : 5 ; each start C'Terminal-A0201-10-terminal-A26-10-mers position is mers Each peptide in a specified, the specified, the Each peptide i's a portion of SEQ ID NO : 9 amino cids, nd portion of SEQ ID N0 : 5 ; each starC position 9 amino acids, and 5 ; each start position is specified, the length each peptide is the IS specifíed, th@ 1ength 1 of peptide i5 10 amino eachSdethe"'''9 P'" ' start position plus of pepbde is 10 amino I acids, and the end start acìds, and the end I position for each position for each peptide is the start peptide is the start position plus nine 14 STIEIGSEI 13 position plus nine 8 PTDSRTSTI 12 13 RTSTIEICSE 3 | DSRTSTIEI | iil RPTDSRTSTI |i W|SVHTRPTDSR|S | TDSRTST1E1 | i| DSRTSTIEIC |g Table XXXI (I 13 RTSTIEICSE 10 PVSVHTRPTD 11 109P1D4v. 2 14 TSTIElCSEI 9 6 HTRPTDSRTS 10 CTermina)-B5101 SVHTRPTDR AHTRPTDSRTS 9-mers- Each peptide is a S|HTRPTDSRTS|E Each peptid-e is a 8n portion of SEQ ID Table XXXIX NO : 5 ; each start TVPVSVHTRPTjfif 109P1D4v. 2 position is specified, C'C'Terminal-B0702 the length of peptide 10-mers is 9 amino acids, I 1I Table 11 is 9 amino acids, Table and the end position portion of SEQ ID N0 : for each peptide is 109P1 D4v, 2 5 ; each start position the start position C'Terminal-is specified, the length plus eight A0203-10-of peptide is 10 amino mers acids, and the end 10 DSRTSTlEI 17 LJ position for each m|RPTi-DSRTST| 1| No Results peptide is the start IPTDSRTSTI F Found. position plus nine 12] 1 14 STIEICSEf 12 Table XXXVII 1 VPVSVHTRPT 18 109P1 D4v. 2-C'8 RPTDSRTSTI 18 Table XXXIV Termina (-A3-10-mers 109P1 D4v. 2 10 TDbRTbHh H 109P1 D4v. 2 Each peptide is a portion of SEQ fD mers NO : 5 ; each start Table XL- Each peptide is a position is specified, 109P1 D4 portion of SEQ ID the length of peptide v. 2 NO : 5 ; each start is 10 amino acids, C'Terminal position is specified, and the end position B08-10- the length of peptide for each peptide is mers is 10 amino acids, the start position plus and the end position nine for each peptide is No the start position plus Results Found. nixe 8) PTDSRTSTIE 16 8 RPTDSRTSTI 12 |S|H_RPTDSRTS HTRPTDSRTSISI Table Table Table XLV)) I-l 09Pl D4v. 2 XLI-XLV-C'Terminal-DRBI 0401 109P1D4 109P1D4 15-mers v. 2 C'v. 2 C'Each peptide is a portion of Terminai-Terminal-SEQ ID NO : 5 ; each start B1510-B5101-position is specified, the length of peptide is 15 amino acids, and the end position for No each peptide is the start, Results position plus fou Found. Found. 1 \lTTFEVPVSVHTRPT 22 Table Table XLVI-109P1D4v. 2 WIFEVPVSVHTRPTDSRIE XL (l- C'Terminal-DR81070 p VHTRPTDSTST (EI 18 lO9PlO4 15-mers v. 2 C'3 TFEVPVSVHTRPTDS 14 Each peptide is a portion of Termina !-SEQ ID NO : 5 ; each starf 5 EVPVSVHTRPTDSRT 94 B2705- 1 0-mers position is specified, the Ell SVHTRPTDSRTSTIE 12 length of peptide is 15 amino acids, and the end position for each peptide is the start 13 RPTDSRTSTIEICSE 12 Results position plus fourteen Found. Tab) eXL) X-109P1D4v. 2 3)) TFEVPVSVHTRPTDSJfl7 C'Termina)-DRB11101 Table 9 S1/HTRPTDSRTSTiE 17 15-mers 1 VTTFEVPVSVHTRPT 6 Each peptide is a portion of 109P9D4 SEQ ID NO : 5 ; each start v. 2 C'S|VPVSVHTRPTDSRTS|S position is specified, the Terminal-| HTRPTDSRTSTIEIC 15 length of peptide is 15 amino 62709--j <-acids, and the end position I 0-mers IPVSVHTRPT H for each peptide is the start ln4 position plus fourteen LJ No RPTDSRTSTIEICSE F- Resutts : 5'EVPVSVHTRPTDSRTjrs'3) TFEVPVSVHTRPTDSJJ25 Found. 5 EVPVSVHTRPTDSRT 15 1'able XLVII-109P1D4v. 2 VTTFEVPVSVHTRPT 13 Table XLIV C'Terminal-DRB1 0301 109P1D4v. 2 15-mers C'terminal-8402-Each peptide is a portion of ae XXf1-109P D4 10-mers SEQ ID N0 : 5 ; each start v. 2-N' terminal-A9-9- mers Each peptide is a position is specified, the portion of SEQ ID length of peptide is 15 amino Each peptide is a NO : 5 ; each start acids, and the end position for portion of SEQ ID position is specified, each peptide is the start NO : 5 ; each start the length of peptide position plus fourteen position is specified, is 10 amino acids, the length of peptide and the end position is 9 amino acids, and for each peptide is ino IVHTRPTDSR the end position for the start position plus each peptide is the nine == : :''==== start position pius ei TFEVPVSVHTRPTDS} jVTTFEVPVSVHTRPTi LIQQT_TSV |E| 8 RPTDSRTSTI 11 14 TSTIICSEI 8 11 QlFQVLCGL 24 8 VL, IQIFQVL 23 15 VLCGLIQQT 22 Table XXV-109P1 D4 Table XXVI El WVLIQIFQV 20 v. 2 N'terminal-A3-109P1 D4v. 2 N' =,. 9-mers terminal-A26-9-mers E I GLIQQVTS E Each peptide is a Each peptide is a 24 VTSVPGMDL 16 portion of SEQ ID portion of SEQ ID 16 LCGLI QTV 14 N0 : 5 ; each start NO : 5 ; each start position is specified, position is specified, the length of peptide the length of peptide 25 TSVPGMDLL 14 is 9 amino acids, and is 9 amino acids, and the end position for the end position for each peptide is the each peptide is the _ J LIQIFQVLC 13 | startpositionplus startpositionplus eight eight Tabfe XXlil-109P1 D4 v. 2 N'terminal-1 L_IQQTVTS 21 29 GMDLLSGTY 9 3 A0201 9-mers 14 QVLCGLIQQ 19 26 SVPGMDLLS 12 Each peptide is a El portion of SEQ ID | m| WVLIQIFQV |S NO : 5 ; each start 26 SVPGMDLLS 16 Table XXVII- position is specified, 109PI D4 the length of peptide v. 2 N'terminal-B0702 is 9 amino acids, and 23 TVT_SVPGMD 14 9-mers the end position for each peptide is the 10 m start position plus 29 GMDLLSGTY 12 portion of SEQ iD eight lRTf=Rnw\/n NO : 5 ; each start eight RTE_RQWVLI 11 p si n is spec f d, the length of peptide 19 LIQQTVTSV 26 g LIQQTVTSV 11 is 9 amino acids, and 11 QIFQVLCGL 24 the end position for each peptide is the 8 VLIQIFQVL 23 Table XX I start position plus 15 VLCGLIQQT 22 109P1D4v. 2 N'eigif n7 2nO terminal-A26-9-mers Each peptide is a 18 GLIQQTVTS 19 Each pepfide is a 24 VTSVPGMDL 16 2n4 NO : 5 ; each start 16 LCGLIQQTV 14 position is specified, 22 QTVTSVPGM 14 the length of peptide 1 MRTERQWVL 11 the end position for each peptide is the F, 11 start position plus B31 LIQIFgVLC 13 starf pesithn plus RTERQWVLI 9 H| VLCGLIQQT |X1 Table 11 QIFQVLCGL 20 17 CGLIQQTVT 8 v. 2 N'41 F16] v. 2 N'4 ERQWVLIQI 16 22 QTVTSVPGM 8 terminal-F A0203 9-mers 22 QTVTSVPGM 16 Table XXVIII 7 WVLIQiFQV 15 o91D4v. 2 N' H terminal-BO8-9-mers No 23 TVTSVPGMD 15 Results Found. 25 TSVPGMDLL 14 RQWVLIQIF 13 Each peptide is a | Table XXX-109P1D4 I Each peptide is a portion of SEQ ID l v. 2 N'terminal-B27051 portion of SEQ ID NO : 5 ; each start 9-mers NO : 5 ; each start position is specified, Each peptide is a position is specified, the length of peptide portion of SEQ ID the length of peptide is 9 amino acids, and NO : 5 ; each start is 9 amino acids, and the end position for position is specified, the end position for each pepffde is the I the lenglh of peptide each peptide is the l start position plus is 9 amino acids, and start position plus ei ht is 9 amino acids, and the end position for each peptide is the eight wight 8 VLIQlFfVL 17 25 i'SVPGMDLL 14 H] j QiFQVLCGT ! fl4-) (. -rr-r. .,.) rr Tt) ERQWVLfQ)) ! l3 | VLIQIFQVL | I | TSVPGMOLL |i 9 MRTER VVVL 25 24 V'i'SVPGMDL 12 5 RQWVLIQIF 93 4 ERQWVLItI D 25 TSVPGMDLDFtO-,,,,,,.--ltQiFQVLCGL FtS 2|WSVPGMDilS GL ERQWVLIQI} 2 | RQWVLIQIF | 11 tiFaVLCGL 17 29 GMDLLSGTY 13 Table XXIX-109PID4 [-IFQ TabieXXiX-109P1D4- w. . ih T)) MRTERQWVLJtl2 v, 2 N'terminal-B1510 VLQfFQVL 16 3 rERQWVtiQ 12 "'''" 9-mers 29 GMDLLSGTY 15 -RQWVLI 11 Each peptide is a 25 TSVPGMDIL 14 portion of SEQ ID RIVTSVPGMDL NO : 5 ; each start position is specified, Table XXXI-109PID4 the length of peptide v. 2 N'terminal-B2709 is 9 amino acids, and 9-mers Table XXXIII the end position for Each peptide is a 109P1 D4v. 2 N' each peptide is the portion of SEQ ID terminal-B5101- start position plus NO : 5 ; each start 9mers position is specified, Each peptide is a the length of peptide portion of SEQ ID 25 TSVPGMDLL 15 is 9 amino acids, and N0 : 5 ; each start the end position for position is specified, each peptide is the the length of peptide El VLIQIFQVL |S start position plus is 9 amino acids, and W31 eight the end position for each peptide is the 11 QlFQVLCGL 11 start position plus S| RQWVLiQiF |S W11 i--RQWVLIQI li19i E| QTVTSVPGM |S..,., 22] F8], IF I RTERQ 13 Table XXX-109P1D4 L. l RQWVLiQiF 12 19 LIQQTVTSV 14 8 VLIQIFQVL 12 v, 2 N'terminal-B2705 0 27 VPGMDLLSG 13 9-mers 11 QfFQVl. CGL 12 1 MRTERQWVL 12 Each peptide is a 25 TSVPGMDLL 12 92 IFQVLCGLI 12 portion of SET IN NO : 5 ; each start lfl F, 61 12 position is specified, 22 QTVTSVPGM 11 7 CGLIQQTVf 12 the length of peptide is 9 amino acids, and the end position for Ta6 (e XXXII 7 WVLIQIFQV 11 each peptide is the 109P1D4v. 2 1' start position plus terminal-B4402-9-8 VLiQiFQVL 1 mers l1 QIFQVLCGL 10 eight 1QQTVTSVP 8 1E1 PGMDLLSGT liS Table XXXIII Table XXXV-109P1D4 Table XXXViI 109P1D4v. 2 N'v. 2-N' terminal-A0201-109P1D4v. 2 N' terminal-B5101-10-mers terminal-A3-10-mers 9mers Each peptide is a Each peptide is a Each peptide is a portion of SEQ ID NO : portion of SEQ ID NO : portion of SEQ ID 5 ; each start position 5 ; each start position NO : 5 ; each start is specified, the length is specified, the length position is specified, of peptide is 10 amino of peptide is 10 amino the length of peptide acids, and the end acids, and the end is 9 amino acids, and position for each position for each the end position for peptide is the start peptide is the start each peptide is the position plus position plus nine start position plus eigh 00 7 WVLIQIFQVL 16 9 LICIFQVLCG 12 H|VTSVPGMDL|E WI VLIQIEQVLC liS W|PGMDLLSGTY|S LIQIFQVLCG [1111 QIFQVLCGLI H|VTSVP§MDLL|S M| CG_IQQTVTS IE Table XXXIV 26 SVPGMDLLSG 15 2 RTERQWVLIQ 10 109P1D4v. 2-N' terminal-A1-10-mers Table Table XXXVIII Each peptide is a -909P1D4v. 2 N' portion of SEQ ID NO : 109PlD4 terminal-A26-10-mers 5 ; each start position v. 2-N' Each peptide is a is specified, the length terminal-portion of SEQ ID NO : of peptide is 10 amino A0203-5 ; each start position is acids, and the end 10-mers specified, the length of position for each peptide is 10 amino peptide is the start acids, and the end position plus nine position for each Results peptide is the start IflIR. RTERQWVLIQ 23 position plus nine g} RTERQW_LIQIg,. I 25 TSVPGMDLLS 16 109P [1D4vX2 N'4 ERQWVLIQIF 22 Fl PGMDLLSGTY 15 29 GMDLLSG_TYI 11 ferminal-A3-10-mers 23 TVTSVPGMDL 22 Each peptide is a 7) WVLIQIFQVL 18 portion of SEQ ID NO : ISVPGMDLLSG Table XXXV-909P1D4 5 ; each start position Tabie XXXV-109P1D4 5 ; each start pos) t) on = L= v. 2-N'terminal-A0201- is specified, the length 11-011 IQIFQVLCGL 16 90-mers of peptide is 10 amino 24 VTSVPGMDLL 16 Each peptide is a acids, and the end 14 QVLCGLIQQT 15 portion of SEQ ID NO : position for each 5 ; each start position peptide is the start 91QTVTSVPGMDIH is specified, the length position plus nine 2 RTERQWVLIQ 13 of peptide is 10 amino PGMDLLSGTY] acids, and the end f SVPGMDLLSGISI position for each peptide is the start E Table XXXIX positionplusnine {VLQIFQVLC {109PID4v. 2N'|| 14 QVLCGLIQQT 17 terminal-B0702-10mer 1 GLIQQTVTSV 29 15 VLCGLIQQTV 16 15 VLCGLIQQTV 25 18 GLIQQTVTSV 16 10 IQIFQVLCGL g LIQQTVTSVP |S| HI QIFQV_LCGLI 17 23 i'Vi'SVPGMDL 14 E| GMDLLSGTYI 17 Each peptide is a Table XLlll Table XLVI-109P1 D4v. 2 portion of SEQ ID NO : 109P1 D4v. 2 N'terminal-DRB1 0101 5 ; each start position is N'terminal-1 15-mers ll specified, the length of B2709- peptide is 10 amino 90mer Each peptide is a portion of acids, and the end position for each position is specified, the length of peptide is 15 amino acids, pepMe s he start NoResuits position plus nine Found. an the end position for each peptide is fhe start position plus fourteen 27 VPGMDLLSGT 7 Table XLIV 7 WVLIQIFQVL 12 109P1 D4v. 2 N' RQWVLIQIFQVLGG 26 0 terminalB4402-10mer 24 VTSVPGMDLL 2 Each peptide is a 1a IQIFQVLCGLIQQTV 26 lno IQIFQVLCGL | I portion of SEQ ID NO : 51 RQWVLIQIFQVLGGL 25 23 TVTSVPGMDL 10 5 ; each start position 13 FQVLCGLIQQTVTSV 24 is specified, the length 16 LCGL) QQTVT) J9 of peptide is 10 amino Hi VLCGLIQQTVTSVPG 23 mjl MRTERQWVL ! 8 acids, and the end 16 LCGLIQQTVTSVPGM 23 3 TERQWVLIQI 8 peptide is fhe st rt LIQIFQVLCGLIQQT 22 15 18 position plus nine HICGLIQQTVTSVPGMD 22 1 GLIQQTVTSV 8] VLIQIFQVLCGLIQQ E|QQTVTSVPGM|X | TERQWVLIQI} 29 GMDLLSGTYI 8 4 ERQWVLIQIF 15 Table XLVII-109P1D4v. 2 0 IQIFQVLCGL 14 N'terminal-DRB1 0301- 15mers Table XL ln3 Table XL 7 WVLIQIFQVL 13 Each e fide is a orfion of N'terminal-SEQ ID NO : 5 ; each start N'terminal- B08-10mers 24 V'fSVPGMDLL 12 position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the start position Found. Table XLV plus fourteen 109P1 D4v. 2 Table XLI N'terminal-Eli RQWVLIQIFQ-VLCGL 109P1 D4v. 2 B5101- N'terminal-10mer 21 QQTVTSVPGMDLLSG 21 B1510- 6 QWVLIQIFQVLCGLI 19 10mer No Results 13 FQVL. CGLIQQTVTSV 17 Found. 191 IFQVLCGLIQ E NoResutts'Y 29) GMDLLSGTYfFAVLL 13 Found. Table XLVI-109P1D4v. 2 LIQIFQVLCGLIQQT 12 N'terminal-DRB1 0101 15-mers 25 TSVPGMDLLSGTYIF 12 Table XLII 27 VPGMDLLSGTYIFAV 12 109P1 D4v. 2 Each peptide is a portion of N'terminal-SEQ ID NO : 5 ; each start 28 PGMDLLSGTYIFAVL 12 82705-position is specified, the length 7 WVLIQIFQVLCGLIQ 91 10mer of peptide is 15 amino acids, and the end position for each LCGLIQQTVTSVPGM peptide is the start position 11 VTSVPGMDLLSGTYI 11 No Results plus fourteen Found. II tounu 1r-, Table XLVIiI-109P1D4v. 2N' 27 VPGMDLLSGTYIFAV 34 terminal-DRB1 0401-15-mers 21 QQTVTSVPGMDLLSG 31 Each peptide is a portion of Table XXII-109P1 D4 Table XX111-109P1D4 SEQ 1D NO : 5 ; each start v. 3-A1-9-mers v. 3-A0201-9-mers position is specified, the length Each peptide is a Each peptide is a of peptide is 15 amino acids, portion of SEQ ID NO : portion of SEQ ID NO : and the end position for each peptide is the start pos tion 7 ; each start position is 7 ; ach start position is pius fourteen specified, the length of | specified, the length of n fer '''"g ' s's"g peptide is 9 amino peptide is 9 amino acids, and the end acids, and the end F13] FQVLCGLIQQTVTsv |E position for each position for each peptide is the start peptide is the start ERQWVLIQIFQVLCG 22 position plus eight position plus eight 10 IQIFQVLGGLIQQTV 22 QWVLIQIFQVLCGLI 20 78 TSHGLPLGY 26 -4 SLTSTSHGL 23 20 GY F7-4 Fgll LIQIFQVLCGLIQQT 20 234 SAQASALCY 23 215 ALHHSPPLV 23 21 QQTVTSVPGMDLLSG 20 135 NCTQECLlY 21 285 GLCSVDQGV 22 27 VPGMDLLSGTYIFAV 20 62 SSDGGLGDH 19 307 RLHPSDDS ! 22 su TERQWVL1QlFQVLC 18 69 DNDAGSLTS 98 203 ALCHS_PPPI 21 14 QVLCGLIQQTVTSVP 18 100 R_TEGDGNSD 18 256 SPLPQVIAl. 21 | RQWVLIQIFQVLCGL 14 106 NSDPESTFI 18 281 QGADGLCSV 21 ml WVLIQlFQVLCGLIQ 14 111 STFIPGLKK 98 238 SALCYSPPL 20 12 IFQVLCGLIQQTVTS 14 83 PLGYPQEEY 17 166 SALCHSPPL 99 16 LCGLIQQTVTSVPGM 14 108 DPESTFIPG 17 190 IALCHSPPV 19 M|CGLIQQTVTSVPGMD|E m|KSEGKVAGK|E E| SALHHSPPL | 29 GMDLLSGTYIFAVLL 14 61 SSSDGGLGD 15 227 ALHHSPPSA 19 g| ASDNCTQEC |g m| HTRPPMKEV |g Table XLIX-109P1D4v. 2 N'2g8 SVDQGVgGS 15 250 AAISHSSPL 18 Terminal-DRB1 1101 15-mers F 19 Each peptide is a portion of 302 YTMSERLHP 15 267 SQAQSSVSL 18 SEQ ID NO : 5 ; each start 310 PSDDSIKVI 15 121 AEITVCPTV 17 position is specified, the length of peptide is 15 amino acids, and the end position for each 145 HSDACWMPA 14 147 DACWMP_ASL 17 peptide is the start position 304 MSERLHPSD 14 178 STQHHSPRV 17 plus fourteen 10 MKEWRSCT 13 191 ALCHSPPVT 17 10 IQIFQVLCGLIQQTV 18 154 SLDHSSSSQ 13 53 HLPEGSQES 16 = VTSVPGMDLLSGTYI 18 13 VTQTIALCH |S | FIPGLKKAA |E E| VTSVPGMDLLSGTYI |E S| ERQWVLIQIFQVLCG |S | VTQTIA_CH |S H| TVQPT_EEA 1S QTiA VQPTYEE -.,., = 256SPLPQViALh3 239 ALCYSPPLA 6 nI CGLIQQTVTSVPGMD IL ! Table XXIII-109P1 D4 274 SLQQGWVQG 16 21 QQTVTSVPGMDLLSG 14 v. 3-A0201-9-mers 314 SIKVIPLTT 16 6 QWVLIQIFQVLGGLI 13 Each peptide is a mI 1 WVLIQI 12 portion of SEQ ID NO : 7) FQVLCGLIQQTVTSV liBi 117 each start posibon is 11 iE <S d = L= speafied, the length of 66) GLGDHDAGSHS EH| GLIQQTVTSVPGMDL 12 peptide is 9 amino M| VPGMDLLSGTYIFAV 12 acids, and the end 29 GMDLLSGTYIFAVLL 12 position foreach 261 VIAl. HRSQA 95 peptide is the start 303 TMSERLHPS 15 position plus eight 6. SQRRVTFHL Table XXllI-109P1 D4 No Table XXV-9 09P1 D4 v. 3-A0201-9-mers 1 Results v. 3-A3-9-mers 1 Each peptide is a Found. Each peptide is a portion of SEQ ID NO : portion of SEQ ID NO : 7 ; each start position is I Table XXV-109P1 D4 7 ; each start position is specified, the length of v. 3-A3-9-mers specified, the length of peptide is 9 amino l peptide is 9 amino acids, and the end Each peptide is a acids, and the end position for each portion of SEQ ID NO : position for each peptide is the start 7 ; each start position is peptide is the start position plus eight specified, the length of position plus eight peptide is 9 amino acids, and the end 6 LGDHDAGSL 4 position for each 234 Sfi, Q_ASALCY 15 70 HDAGSLTST 4. peptide is the star posiCion plus eight VVRStTPM 14 81 GLPLGYPQE 14 40 GKVAGKSQR 14 109 PESTFIPGL 14 3 SVNTRPPMK 25 49 RVTFHLPEG 14 116 GLKKAAEiT -twRSCTPMK EWEGSQE F I GL. KKALEIT 14 ES| SLDHSSSSQ) S ='SLKKAAEiT 194 HSPPVT_QTf 14 23 ALH_RSQAQS 22 122 EITVQF'TVE 14 263 ALHRSQ_AQS 14 41 KVAGKSQRR 21 162 QAQ_ASALCH 14 278 GWVQG_ADGL 14 274 SLCQGWVQC 20 167 ALCHSPPLS 14 312 DDSIKV_IPL 14 316 KVIPLTTFT 20 23 ALCHSPPPI 14 tSTSHGLPLG (KSEGAGK tALHHSPPLV 117 LKKAAEITV 13 26Q QVIALHRSQ 99 39 ALCYSPPLA 14 KAAE. TVQP jSVSLQaGWVJ 120 AAEITVQPT 13 111 STFIPGLKK 18 45 KSCRRVTFH 13 123 iTVQPTVEE 13 140 CLIYGHSDA 18 53 HLP_EGSQES 13 133 SDNCTgECL 3 173 PLSQASTQH 18 92 FDR_ATPSNR 13 160 SSQAQA_SAL 13 g ALCNSPPVT 18 124 TV_QPTVEEA 13 | ALCHSePLS |g | PIQVS_HH | | TIALCHSPP lS 205 CHSPPPIQV 13 257 PLP_QVIALH 18 97 PQTlALC 13 217 HHSPPLVQA 13 gg2 GVCGSATSQ 18 201 TIA_LCHSPP 13 |CYSPPLAQA|g Ej| Sl_VIPLTT |M |RSQAQSSVSt 257 PLPQVIALH 13 7 RPPMKEVVR 17 279 WVgGADGLC 13 BILQQGWYQGAIlE | RVTQTLLC |E | SVDQGVQGS |S |SVDQGYQGS|S | PL QA_LH | | LHPSDDSIK | Et SDDSiKV PLAQAM. S M LTTFTP 317 VIPLTTFTP 13 261 VIALHRSQA 97 Table XXVI-I 09P I D4 Table v, 3-A26-9-mers XXIV-8 GLPLGYPQE 16 Each peptide is a 109P1D4 E| PLGYPQEyl portion of SEQ ID NO : v. 3- 154 SLDHSSSSQ 16 7 ; each start position is A0203-9-22 QVSALHHSP 6 specified, the length of mers 0 peptide is 9 amino 227 ALHHSPPSA 16 acids, and the end position for each Peptide is the start EH| LIYGHSDAC 15 position plus eight . Table XXVI-109P1D4 Table XXV11-109P1D4 12 EVVRSCTPM 24 v. 3-A26-9-mers v. 3-B0702-9-mers Each peptide is a Each peptide is a portion of SEQ ID NO : portion of SEQ ID NO : 147 DACWMPASL 17 7 ; each start position is 7 ; each start position is 395 ICVIPLTTF 7 specified, the length of specified, the length of peptide is 9 amino peptide is 9 amino cids, nd h end cid, nd the end 124 TVQPTVEEA liRi position for each position for each peptide is the start peptide is the start =="="== position p ! us eight position pius eight 260 QVIALHRSQ 16 313 DSIKVIPLT 16 Og PESTFIPGL 12 PPMKEWRS 15 316 KVIPLTTFT 16 123 ITVQPTVEE 12 7 RPPMKEVVR 14 335 DSPMEEHPL 16-=-= : = 335 DSPMEENPL 16 130 EEASDNGTQ 12 76 TSTSHGLPL 14 | RVTFHLPEG |g | NCTQECLIY |i | lPGLKKME |i S| EYFDRATPS |g 31 EGLIYGHSD 1g S|CHSPPVTQT|i jr EITVQPTVE |M H| QVSALHHSP |S S|HHSPPLVQA|S lF2-21 2-17 EM| PTVEEASDN |h S| SAQASALCY |E H| DDSlKVlPL liS 136 CTQECLIYG 15 272 SVSLQQGWV 12 318 IPI. TTFTPR 14 B| RVTQTIALC |g |GWVQGADGL|E gj|SQRRVTFHL|g 197 PVTQTIALC 15 96 TPSNRTEGD 13 288 SVDQGVQGS 15 TabIeXXVfI-109P1D4 109 PESTFIPGL 13 STTMEiWiH v. 3-B0702-9-mers 229 NHSPPSAQA 13 24 TTMEIW1HP 14 Each peptide is a 27 EIWIHPQPQ 14 portion of SEQ lD N0 : 241 CYSPPLAQA 13 7 ; each start position is F specified, the length of 267 SQAQSSVSL 13 1 4 PRVTQTIAL 14 peptide is 9 amins iw31 ; i acids, and the end l EiEM3EG 196 PPVTQT1AL 14 p ptide 1s the st rt L 1 NTRPPMKEV 12 | QTIALCHSP IE ! positionpluseight il S|LPEGSQESS|S 208 PPPIQVSAL 14 54 LPEGSQESS 12 S AAISHSSPL 14 232 PPSAQASAL 24 5g QESSSDGGL 12 321 TTFTPRQQA 14 256 SPLPQVIAL 23 pg DPESTF PG 12 50 VTFHLPEGS 13 196 PPVCQTIAL 22 -' 60 ESSSDGGLG 13 208 PPPIQVSAL 22 160 SSQAQASAL 12 000 166 SAL. CHSPPL 12 F5-ol F, 9-6] Fl-60] 19 E| TSTSHGLPL | S PPLVQATAL | Hj|CHSPPLSQAlS 77 STSNGLPLG 13 330 RPSRGDSPM 20 84 PRVTQTIAL 12 78 TSHGLPLGY 13 18 TPMKESTTM 19 205 CHSPPPIQV 12 128 TVEEASDNC 18 13 SPRVTQTIA 19 214 SALHHSPPL 12 131 EASDNCTQE 13 207 SPPPIQVSA 19 238 SALCYSPPL 12 284. DGl. CSVDQG 13 244 PPLAQAAAI 19 253 SHSSPLPQV 12 m| SVHTRPPMK 12 243 SPPLAQAAA 18 EE| VVRSCTPMK |S S| HPSDDSIKV |Ri 22 ESTTMEIWI 12 71 SPPLSQAST 17 Table XXVIII-109P1D4 39 EGKVAGKSQ 12 195 SPPVTQTIA 17 v. 3-BO8-9-mers 56 EGSQESSSD 12 219 SPPLVQATA 17 71 DAGSLTSTS 12 231 SPPSAQASA 17 Each peptide is a Table XXVIII-109P1D4 Table XXIX 109P1D4 portion of SEQ ID NO : v. 3-B08-9-mers v. 3-B1510-9-mers 7 ; each start position is Each peptide is a Each peptide is a specified, the length of portion of SEQ ID N0 : portion of SEQ ID NO : peptide is 9 amino 7 ; each start position is 7 ; each start position is acids, and the end specified, the length of specified, the length of position for each peptide is 9 amino I peptide is 9 amino peptide is the start acids, and the end acids, and the end position plus eight position for each position for each peptide is the start peptide is the start 312J DDSiKVtPL 2 ? position p) us eight position plus eight 256 SPLPQVIAL 20 bol IPGLKKME | |GWQGADGL|E | QFYTMSERL |g 46 SQRRVTFHL 8 312 DDSIKVIPL 12 74 SLTSTSHGL 18 Table XXIX-09P1D4 59 QESSSDGL 11 D0° Ea h1pept de s a 76 TSTSHGLPL 11 208 PPP1QVSAL 18 =====."= Eachpephdosa 70) c :)-) rt p) rvp iFTt lit PPLVQATAL 18 portion of SEQ ID NO : 79 SHGLPLGYP 11 | RPPMKEVVR IE 7 ; each start position is I PGLKKAAEI 17 specified, the length of 147 DACWMPASL 11 160 SSQAQASAL 11 116 GLKKAAEIT 7 acdsandth end 196 PPVTQTIAL 17 position for each 166 SALCHSPPL 11 peptide is the start gq. PRVTQTIAL 11 F23-2] PPSAQASAL 17 position plus eight 314)) SIKVIPLTT | | PPVTQTIAL IE Sil QPQRKSEGK 16 30 IHPQPQRKS 16 214 SALNNSPPL 11 44 GKSQRRVTF 16 291 HHSPPLVQA 16 3$ SALCYSPPL 11 166 SALCHSPPL 16 180 QHHSPRVTQ 15 6 SQRRVTFHL 10 214 SALHHSPPL 16 193 CHSPPVTQT 15 67 LGDHDAGSL 10 238 SALCYSPPL 16 205 CHSPPPIQV 15 74 SLTSTSHGL 90 183 SPRVTQTIA 15 169 CHSPPLSQA 14 133 SDNCTQECL 10 EGKVAGKSQ 14 181 HHSPRVTQT 14 250 AAISHSSPL 10 96 TPSNRTEGD 94 216 LHHSPPLVQ 14 264 LHRSQAQSS 10 147 DACWMPASL 14 229 HHSPPSAQA 14 308 LNPSDDSlK 10 250tAAiSHSSPL fl4 ''TF 262 IALHRSQAQ 14 267 SQAQSSVSL 14 335 DSPMEEHPL 10 S| PMKEVVRSC |S H| GKSQRRVTF |S} TPMKESTTM} E 160 SSQAQASAL 13 109 PESTFIPGL 13 VSVHTRPPM 8 244 PPLAQAAAI 13 144 GHSDACWMP 13 $4 LGYPQEEYF 8 267 SQAQSSVSL 13 228 LHHSPPSAQ |g S| RPSRGDSPM | Ei| PMKESTTME 12 253 SHSSPLPQV 13 133 SDNCTQECL 12 278 GWVQGAGL 13 Table XXX-109P1D4 X| ALCHSPPPI lS m| VHTRPPMKE 1E I Each peptide is a 307 RLHPSDDSI 12 52 FHLPEGSQE 12 portion of SEQ ID NO : 32A. TPRQQARPS 12 69 DHDAGSLTS 12 7 ; each start position is 35 QfKSEGKVA SPpped, the length of 156 DHSSSSQAQ 12peptide is 9 amino 3'l KSEGKVAGK 11 208 PPPIQVSAL 12 acids, and the end position for each peptide is the start position plus eight Table XXX 109P1 D4 325 PRQQARPSR 24 v. 3-B2705-9-mers 184 PRVTQTIAL 21 184 PRVTQTIAL 22 Each peptide is a 6 TRPPMKEW 19 portion of SEQ fO NO : 40 GKVAGKSQR 19 7 ; each start position is 265 HRSQAQSSV 118 278 GWVQGADGL 19 specified, the length of 28 GWVQGADCL 5 EHPQPQR S M] ! GWQGADGL i3lKVAGKSQRRlg | positionforeach l S| SPLPQVIAL |E F7-171 pept (de is the start 76 TSTSHGLPL 13 37 KSEGKVAGK 17 Pfiion plu ight F-F Fl-6 6 13 F44]-S-ALHHSPPL] 13 slFPG3 g 3 L { 13] F2 l4F 92 FDRATPSNR 13 315 fKV (PLTTF 17 238 SALCYSPPL 13 137 TQECLIYGH 13 EX| RRVTFHLPE 16 5g LPQVIALHR 13 250 AAISHSSPL 13 99 NRTEGDGNS 16 300 QFYTMSERL 13 312 DDSlKVlPL 13 105 GNSDPESTF 16 307 RLHPSDDSI 13 322 TFTPRQ R 13 265 HRSQAQSSV 16 332 SRGDSPMEE 93 I""''1 SQRRVTF 12 267 SQAQSSVSL 16 67 LGDHDAGSL 12 12 EVVRSCTPM 12 Xl TPMKESTTM lM | QRKSEGKVA |E S| NRTEGDGNS |S 18 TPMKESTTM 15 35 QRKSEGKVA 12 99 NRTEGDGNS 12 X| PPIQVSALH 15 190 IALCHSPPV 12 | PPLVQATAL |S E| TSHGLPLGY |S E| ERLHPSDDS |S 67 LGDHDAGSL 12 220 PPLVQATAL 15 7g TSHGLPLGY 12 306 ERLHPSDDS 12 M| PLPQVIALH |S Nl SDNCTQECL lS EI QRKSEGKVA IE [300 Fl-47 86 YPQEE FDR 12 [72] IF051 F,-o 91 iFo-91 F, 11 135 NCTQECLIY 12 300 QFYTMSERL 15 4. LGYPQEEYF 11 147 DACWMPASL 12 318 IPLTTFTPR 15 93 DRATPSNRT 19 160 SSQAQASAL 12 H| IPLTTFTPR 14 196 PPVTQTIAL 12 105 GNSDPESTF 11 E [m3i H<S HME | PGLKKAAEI |E E| PLVQATALH lS Eil PGLKKAAEI IE 166 SALCHSPPL 14 121 AEITVQPTV 11 232 PPSAQASAL 12 173 PLSQASTQH 14 943 YGHSDACWM 11 177 ASTQHHSPR 14 293 VQGSATSQF 12 960 SSQAQASAL Rl 308 LHPSDDSIK 12 214 SALHHSPPL 14 3g ARPSRGDSP 12 196 PPVTQTIAL 11 i| SALCYSPPL 14 208 PPPIQVSAL 11 H| ERLHPSDDS 14 232 PPSAQASAL 11 Tab (e XXXf-109P1 D4 307 RLHPSDDSI 14 v. 3-B2709-9-mers || HI PPLAQAMI IE IN Each peptide is a 253 SHSSPLPQV 11 6 TRPPMKEVV 13 portion of SEQ ID NO : 2671 7 ; each start position is F specified, the length of 00 23 STTMEIWIH 13 peptide is 9 amino 312 DDSIKVIPL 11 13 acids, and the end position for eacn peptide is the start position plus eight Table XXXII Each peptide is a Table XXXIII 109P1D4v. 3-B4402- portion of SEQ ID NO : 109P1D4v. 3-B5101 9-mers 7 ; each start position is 9-mers Each peptide is a specified, the length of Each peptide is a peptide is 9 amino portion of SEQ ID NO : portion of SEQ ID N0 : P acids, and the end 7 ; each start position is 7 ; each stari position osition for each is specified, the length p specified, the length of peptide i the start peptide i 9 amino of peptide i 9 mino osilion lu ei ht acids, and the end p p g acids, and the end position for each position for each peptide is the start 244 PPLP, I 24 peptide is the stark position plus eight position plus eight 42 VAGKSQRRV 23 109 PESTFIPGL 2 7 DACWMPASL 22 7 LKKAAEiTV 14 CALCHSPP 59 QESSSDGGL 21 309 HPSDDSIKV 22 202 IALCHSPPP 14 256 SPLPQVIAL 19 115 PGLKKAAEI 21 234 SAQASALCY 14 LKKAAEi 4 LVQATALS 238 S LCYSPPL 19 28 GADGLCSVD 14 F Fl 51 F16-6] 18 44 GKSQRRVTF 15 166 SALCNSPPL 18 2 EST'TMEIWI 13 1ALCHSPPL@ 196 PPVTQTfAL 15 SALHHSPPL 18 g , qETVQP 93 SAQASAL 160) SSQAQASAL) [14 3 JPLTTFTPR M 12) AEiTVQPTV) tl3 194HHSPPVTQTi) fl4 LPLGYPQEE 195)) SPPVTQTiA) tl3 E é g i I Table OWV ----- 9 95] 94 HSPPVTQTI] ln4 F, IF Fl 0-8] F, [2-0-81 H F22-6] == = 2-54] El m 3FO-0] E ES CTQECU = 78 TSHGLPLGY 13 $ TPM4fESTTM 15 z F7-8] 13 12 130EEASDNCT3 =-= 203 ALCHSPPpH2 === = = 194 HSPPVTQTi 15 == = 234AQASALCYF) 3 ="= 207 SPPPiQVSA) 2 ----'''' 219 SPPLVQATA 15----- 234 SAQASALGY 13 94 HSPPVTQTI 15 a07 SPPPIQVSA 12 F, 3-0] Fl-8 2] IN F2-031 "'''E r') 258 LPQVIALHR 15 Table XXXlV EjDGLCSVDQG| 1OgP1D4v. 3-A1 109P1 D4v. 3-B5101 6 TRPPMKEW 14 10-mers 9-mers 54 LPEGSQESS 14 S3 j YPQEEYFDR | Each peptide is a Table XXXV-109P1D4 Table XXXV 109P1D4 portion of SEQ ID NO : v. 3-A0201-10-mers v. 3-A0201-10-mers 7 ; each start position is Each peptide is a portion Each peptide is a portion specified, the length of of SEQ ID NO : 7 ; each of SEQ ID NO : 7 ; each peptide is 10 amino start position is specified, start position is specified, acids, and the end the length of peptide is the length of peptide is position for each peptide 10 amino acids, and the 10 amino acids, and the posmon) or each pepMe g, g J gj g g g is the start position plus end position for each end position for each nine peptide is the start peptide is the start position plus nine position plus nine 78 STSHGLPLGY 29 234 PSAQASALCY 25 6 HTRPPMKEVV 16 241 LCYSPPLAQA 13 135 DNCTQEGLIY 21 20 PMKESTTMEI 16 244 SPPLAQ_41 13 E|SSDGGLGDHD|B | STFIPGLKKA |g El TMSERLHPSD |g 101 RTEGDGNSDP 18 124 ITVQPT_VEEA 16 25 TTMEIWIHPQ 12 107 NSDPESTFIP 18 155 SLDHSSSSQA 16 30 WIHPQPQRKS 12 3 KSEGKVAGKS 17 192 ALCHSPPVTQ 16 34 QPQRKSEGKV 12 312 SDDSIKVIPL 17 312 SDDSIKVIPL 16 59 SQESSSDGGL 12 83 LPLGYPCEEY 16 74 GSLTSTSHGL 15 133 ASDNCTQECL 12 294 V_QGSATSQFY 16 142 LIYGHSDACW 15 137 CTQECLIYGH 12 |ASDNCTQECL|M | ASALCHSPPL lB El CLIYGHSDAC |S 168 ALCHSPPLSQ 15 178 ASTQHHSPRV 12 TabIeXXXV-109P1D4 238 ASALCYSPPL 15 182 HHSPRVTQTI 12 v. 3-A0201-10-mers I 315 SIKVIPLTTF 15 194 CHSPPVTQTI 12 Each peptide is a portion 54 HLPEGSQESS 14 205 LCHSPPPIQV 12 of SEQ ID NO : 7 ; each- start position is specified, 109 DPESTFIPGL 94 217 LHHSPPLVQA 12 the length of peptide is 114 FIPGLKKAAE 14 257 SPLPQVIALH 12 10 amino acids, and the end position for each 115 IPGLKKAAEI 14 262 VIALHRSQAQ 12 peptideisthestart E31 VSALHHSPPL IEF |SSVSLQQGWV1g position plus nine 264 ALHRSQ_AQSS 14 278 QGWVQGADGL 12 265 LHRSQAQSSV 14 285 DGLCSVDQGV 12 67 GLGDHDAGSL 24 267 RSQAQSSVSL 14 289 SVDQGVQGSA 12 117 GLKKAAEITV 22 309 LHPSDDSIKV 14 300 SQFYTMSERL 12 190 TIALCHSPPV 21 | GDSPMEEHPL 14 303 YTMSERLHPS 12 275 SLQQGWVQGA 21 g2 GLPLGYPQEE 13 308 RLHPSDDSIK 12 | KVAGKSQRRV lE Hl SSSQAQASAL lS H| HPSDDSIKVI |S 20 SPPPIQVSAL |E El SPRVTQTIAL lD SALHHSPPLV 19 191 IALCHSPPVT 13 Table XXXVI 121 AAEITVQPTV 18 196 SPPVTQ_TIAL 13 109P o mers 03 147 SDACWMPASL 18 204 ALCHSPPPIQ 13 Each peptide is a 9 AAA) HPi RH ==-LJ Eachpephdesa OU/W\rOOrL ho OIR A !)-))-) C ! DD] \/r m-i'rt-))- ! 250 AAAISHSSPL 18 216 ALNHSPPLVQ 13 portion ofi SEQ ID N0 : 76 LTSTSHGLPL 17 220 SPPLVQATAL 9 7 ; each start position is 120 KAAEITVQPT 17 2 7 TALHHSPPSA 1 Spepidedishe0 amino of peptide is 10 amino 9fn ! Ai rnc ; ppp ! Fy == = pepMe ! suam ! no 203 IALCHSPPP) 17 g p, LHHSPPSAQ 13 acids, and the end 253 ISHSSPLPQV 17 232 SPPSAQASAL 13 position for each 256 SSPLP (VIAL 17 peptide is the start 0 239 SALCYSPPLA 13 position plus nine === = 239 SALCYSPPLA)) 13 poson plus n) ne 281 VQGADGLCSV 17 240 ALCYSPPLAQ 13 Tabi XXXVI Table XXXVII Table XXXVIII 109P1 D4v. 3-A0203 109P1 D4v. 3-A3 109P1 D4v. 3-A26 10-mers 10-mers 10-mers Each peptide is a Each peptide is a portion Each peptide is a portion portion of SEQ ID NO : of SEQ ID NO : 7 ; each of SEQ ID NO : 7 ; each 7 ; each start position is start position is start position is specified, the length of specified, the length of specified, the length of peptide is 10 amino peptide is 10 amino peptide is 10 amino acids, and the end acids, and the end acids, and the end position for each position for each peptide position for each peptide peptide is the start is the start position plus is the start position plus position plus nine nine nine I I 243 YSPPl_QAAA 27 258 PL_PQVIALHR 20 3 EVVRSGTPMK 25 113 TFIPGLKKAA 19 168 ALCHSPPLSQ( 19 109 DPESTFIPGL 2 S|C_SPPLAQAA|S B|SV_LQQWVQ|S E| STSHGLPLGY |E E2|DHSSSSQAQA|R H| SIKVIE_TTF |S W|GVQGSATSQF|E 959 SSSSQAQASA 18 37 RKSEGKVAGK 18 105 DGNSDPESTF 19 219 HS_PPLV (ATA 18 228 ALH_HSPPSAQ 18 135 DNCTQECLIY 19 229 LHHSPPSAQA 18 240 ALCYSPPLAQ 18 76 LTSTSHGLPL 18 E|HSPPSAQASA|B S|WVQGADGLCS|M S| STFIPGLKKA |S | LCYSPPLAQA |g i| AG_SQRRVTF |g | SIKVIPLTTF | 114 FIPGLKKAAE 17 67 GLGDHDAGSL 17 91 EYFDRATPSN 16 244 SPPLAQAAAAI 17 142 LIYGHSDACW 17 124 ITVQPTVEEA 16 155 SLDHSSSSQA 17 208 SPPPIQVSAL 16 Table XXXVII 213 QVSALHHSPP 17 261 QVIALHRSQA 16 109P1D4v. 3-A3 28 EIWIHPQPQR 16 317 KVIPLTTFTP 16 10-mers- Each peptide is a portion 29 IWIHPQPQRK 16 23 ESTTMEIWIH 15 Each pephde) s a port ! on-'- == of SEQ ID NO : 7 ; each 42 KVAGKSQRRV 1E 25 TTMEIWIHPQ 15 start position is 111 ESTFIPGLKK 16 28 EIWIHPQPQR 15 specified, the length of 7 TRPPMKEWR 15 123 EITVQPTVEE 15 peptide is 10 amine- acids, and the end 14 VVRSCTPMKE 15 256 SSPLPQVIAL 15 position for each peptide is the start position plus nine 117 GLKKAAEITV 15 51 VTFHLPEGSQ 14 S| Al_HSSPLPQ |M H| ESTFIPGLKK 1i 308 RLHPSDDSIK |} GLCSVDQGVQ|g | PTVEEASDNC |i 13 EVVRSCTPMK 24 137 CTQECLIYGH 14 186 RVTQTIALCH 24 Table XXXVIII 223 LVQATALHHS 14 109P1D4v. 3-A26 314 DSIKVIPLTT 14 261 QVIALHRSQA 24 10-mers | KV1PLTTFTP | {Each peptide is a portion | TTFTPRQQAR IES3 Ell ALCHSEPVTQ |W of SEQ ID NO : 7 ; each GVSGSAISQF i 293 GVQ_GSATSQF 22 start position is 70 DNDAGSLTST 13 216 ALHHSPPLVQ 21 spciFed, the length ofi peptide is 10 amino 125 TVQPTVEEAS 13 264 ALHRSQAQSS 21 acids, and the end 198 PVTQTIALCH 20 posifiion fior each peptide gg QTIALCHSPP 3 is the start position plus 222 PLVQATALHH 20 nine 201 QTIALCHSPP 13 ex PLA_QAAAISH 20 289 SVDQGVQGSA 13 Table XXXVIII Table XXXIX Table XLII 109P1 D4v. 3-A26 109P1 D4v. 3-B0702 109P1 D4v. 3- 10-mers 10-mers B2705 Each peptide is a portion Each peptide is a 10-mers of SEQ ID NO : 7 ; each portion of SEQ ID NO : start position is 7 ; each start position is No Results specified, the length of specified, the length of Found peptide is 10amino peptide is 10amino'=' acids, and the end acids, and the end position for each peptide position for each peptide Table XLIII position plus is the start position plus 109P1 D4v. 3- nine nine B2709 10-mers 300 SQFYTMSERL 13 335 GDSPMEEHPL 14 U 303 YTMSERLHPS ln3 S| PPMKEWRSC |g < ES|ASDNCTQECL |S Table XXXIX 160 SSSQAQASAL l3 109Pl D4v. 3-B0702 214 VSALHHSPPL 13 Table XLIV-109P9 D4 10-mers v. 3-B4402-10-mers Each peptide is a 312 SDDSIKVIPL 13 Each peptide is a portion portion of SEQ ID NO : 319 IPLTTFTPRQ 13 of SEQ ID N0 : 7 ; each 7 ; each start position is 1 VPVSVHTRPP 12 start position is specified, specified, the length of the length of peptide is peptide is 10 amino 46 KSQRRVTFHL 12 10 amino acids, and the acids, and the end 55 LPEGSQESSS 12 end position for each position for each peptide g3 LPLGYPQEEY 12 peptide is the start is the start position plus 0 position plus nine ! S the start pos ! hon ptus == = pob ! uonp) ubn ! ne nine 97 TPSNRTEGDG 12 147 SDACWMPASL 12 22 KESTTMEIWI 22 184 SPRVTQTIAL 24 210 PPIQVSALHH 12 122 AEITVQPTVE 19 208 SPPPIQVSAL 23 221 PPLVQATALH 12 208 SPPPIQVSAL 18 196 SPPVTQTIAL 22 245 PPLAQAAAIS 12 256 SSPLPQVIAL 17 220 SPPLVQATAL 22 256 SSPLPQVIAL 12 44 AGKSQRRVTF 6 ES| DPESTFIPGL 21 257 SPLPQVIALH 12 196 SPPVTQTIAL 16 232 SPPSAQASAL 21 220 SPPLVQATAL 16 115 IPGLKKAAEI 19 Table XL 310 HPSDDSIKVI 16 HPSDDSIKVI |S| 11 B08 11 ||ASDNCTQECL |S| 244 SPPLAQAAAI | 10-mers | SSSQAQASAL |S| 87 YPQEEYFDRA 17 184 SPRVTQTIAL 15 34 QPQRKSEGKV 16 No Results 232 SPPSAQASAL 15 76 LTSTSHGLPL 15 Found. 335 GDSPMEEHPL 15 F16-611 ASALCHSPPL 15 27 MEIWIHPQPQ 14 238) ASALCYSPPL 15 1 9P1 D4v. 13- 78 STSHGLPLGY 14 8 RPPMKEVVRS 14 B1510 110 PESTFIPGLK 14 9 TPMKESTTME 14 10-mers 166 ASALGHSPPL 14 2373 PPSAQASALC 14 182 HHSPRVTQTI 14 250 AAAISHSSPL 14. No Results g4 GHSPPVTQTI 14 267 RSQAQSSVSL 14 Found. 238 ASALCYSPPL 14 325 TPRQQARPSR 14 244 SPPLAQAAAI l4 331 RPSRGDSPME 14 312 SDDSIKVIPL 14 Table Xl. IV-109P1 D4 Table Table XLVI-109P1 D4v. 3- v. 3-B4402-10-mers XLV-DRB1 0101-15-mers 109P1D4 Each peptide is a portion Each peptide is a portion of SEQ of SEQ ID NO : 7 ; each iD NO : 7 ; each start position is start position is specified, specified, the length of peptide is the length of peptide is 10-mers 15 amino acids, and the end 10 amino acids, and the position for each peptide is the end position for each start position plus fourteen peptide is the start Results position plus nine Found. 55 RVTFHLPEGSQESSS 20 270 LHRSQAQSSVSLQQG 20 39 SEGKVAGKSQ 13 Table XLVI-109P1 D4v. 3- 2g STTMEIWIHPQPQRIf 19 46 KSQRRVTFHL 13 DRB 0101-15-mer 116 ESTFIPGLKKAAEIT 119 74 GSLTSTSHGL 13 Each peptide is a portion of SEQ-- LTSTSHGLPL] ID NO : 7 ; each start position is F specified, the length of peptide is 326 LTTFTPRQQARPSRG 19 90 EEYFDRATPS] 3 15 amino acids, and the end 109) DPESTFIPGL 13 position for each peptide is the 93 PQEEYFDRATPSNRT 18 - EEASDNCTQE |i start position plus fourteen fol53) L DACWMPASLDHSSSS IEG S| AAAISHSSPL 13 278 SVSLQQGWVQGADGL 18 AAAISHSSPLI I F 293 GVQGSATSQF 13 320 SIKVIPLTTFTPRQQ 30 291 GLCSVDQGVQGSATS 18 S |SQFYTMSERL| E |QRRVTFHLPEGSQES| E |RQQARPSRGDSPMEE|R H| SiKViPLTTF" CDYGHSDACWMPAS T1 TFEVPVSVHTRPPMKtl7 60 QESSSDGGLG 12 245 ALCYSPPLAQAAAIS 26 17 KEVVRSCTPMKESTT 17 g| GLGDHDAGSL | E|LQQGWVQGADGLCSV|E E| RSCTPMKESTTMEIW |E X11 LPLGYPQEEY 12 33 EIWIHPQPQRKSEGK 24 41 QRKSEGKVAGKSQRR 17 E| QEEYFDRATP |g m| DGGLGDHDAGSLTST | E| RKSEGKVAGKSQRRV | iB| DNCTQECLIY |S S| PIQVSALHHSPPLVQ |E | EGKVAGKSQRRVTFH |E IF3511 QECLIYGHSD 12 223 HHSPPLVQATALHHS 24 67 SSSDGGLGDNDAGSL 17 147 SDACWMPASL 12 264 LPQVIALHRSQAQSS 24 78 AGSLTSTSHGLPLGY 17 234 PSAQASALCY 12 267 VIALHRSQAQSSVSL 24 914 DPESTFIPGLKKAAE 17 254 SHSSPLPQVI 12 283 QGWVQGADGLCSVDQ 24 198 TFIPGLKKAAEITVQ 17 306 SERLHPSDDS 12 318 DDSIKVIPLTTFTPR 24 189 SPRVTQT (ALCHSPP 17 EE| KEWRSCTPM 11 23 CTPMKESTTMEIWIH 23 201 SPPVTQTIALCHSPP 17 TQT. ALCHSPPVTQT 23 SPPLVQATALHHSP 102 TEGDGNSDPE 11 205 TQTIALGHSPPPIQV 23 228 LVQATALHHSPPSAQ 17 -1 F276 IQSSVSLQQGWVQGADI 23 1 CYSPPLAQ Eg| VEEASDNCTQ | m| TTFTPRQQARPSRGD | E| AQAAA1SHSSPLPQV |E E| LIYGHSDACW |E m| FEVPVSVHTRPPMKE | |AQSSVSLQQGWVQGA|M 214 VSALHHSPPL 11 38 PQPQRKSEGKVAGKS 22 304 TSQFYTMSERLHPSD 17 267 RSQAQSSVSL 11 158 PASLDNSSSSQAQAS 22 309 TMSERLHPSDDSIKV 17 YSPPLAQAAA. SH22 = VTTFEVPVSVHTR 278 QGWVQGADGL 11 261 SSPLPQVIALHRSQA 22 5 EVPVSVHTRPPMKEV 16 Mi ERLHPSDDSI 11 296 DQGVQGSATSQFYTM 22 32 MEIWIHPQPQRKSEG 16 axe AAEITVQPTVEEASD 21 50 GKSQRRVTFHLPEGS 16 294 SVDQGVQGSATSQFY 21 57 TFHLPEGSQESSSDG 16 305 SQFYTMSERLHPSDD 21 77 DAGSLTSTSHGLPLG 16 E4 PPMKEWRSCTPMKE 20 79 GSLTSTSHGLPLGYP 16 Table XLVI-109P1 D4v. 3- Table XLVI-109P1 D4v. 3- Table XLVII-109P1 D4v. 3 DRB1 0901-15-mers DRB1 0101-15-mers DRB1 0301 15-mers Each peptide is a portion of SEQ Each peptide is a portion of SEQ Each peptide is a portion of ID NO : 7 ; each start position is ID NO : 7 ; each start position is SEQ ID NO : 7 ; each start specified, the length of peptide is specified, the length of peptide is position is specified, the length 15 amino acids, and the end 15 amino acids, and the end of peptide is 15 amino acids, position for each peptide is the position for each peptide is the and the end position for each start position plus fourteen start position plus fourteen peptide is the start position plus fourteen 82 TSTSHGLPLGYPQEE 96 142 CTQECLIYGHSDAC1N 15 87 GLPLGYPQEEYFDRA 16 156 WMPASLDHSSSSQAQ 15 120 IPGLKKAAEITVQPT 17 94. QEEYFDRATPSNRTE 16 169 AQASALCHSPPLSQA 15 264 LPQVIALHRSQAQSS 97 95 EEYFDRATPSNRTEG 6 18) SQASTQHHSPRVTQT 15 289) ADGLCSVDQGVQGSA) H| GDGNSDPESTFIPGL |g M} QHHSPRVTQTIALCH |g ILTTFTPRQQARPSRGIE EM| STFIPGLKKAAEITV |g | LCHSPPVTQTIALCH |g SLEVPVSVHTRPPMKEV|E 128 EfTVQPTVEEASDNC 16 212 HSPPPIQVSALHHSP 15 292 LCSVDQGVQGSATSQ 16 141 NCTQECLIYGHSDAC 16 217 IQVSALNNSPPLVQA 95 304 TSQFYTMSERLHPSD 16 954 ACWMPASLDHSSSSQ 16 229 VQATALHHSPPSAQA 15 7$ AGSLTSTSHGLPLGY 14 155 CWMPASLDHSSSSQA 16 241 AQP, SALCYSPPLAQA 15 136 EASDNCTQECLIYG 14 161 LDHSSSSQAQASALC 16 265 PQVIALHRSQAQSSV 15 17 KEWRSCTPMKESTT 13 163 HSSSSQP, QASALCHS 16 312 ERLHPSDDSIKVIPL 15 64 SQESSSDGGLGDHDA 13 168 QAQASALCHSPPLSQ 16 69 SDGGLGDHDAGSLTS 13 187 HHSPRVTQTIALCHS 16 Table XLVII-109P1 D4v. 3 126 AAEITVQPTVEEASD 13 192 VTQTIALCHSPPVTQ 16 I DRB1 030115-mers 132 QPTVEEASDNCTQEC 13 204 VTQTIALCHSPPPIQ 16 Each peptide is a portion of 243 ASALCYSPPLAQAAA 13 0 SEQ ID N0 : 7 ; each st rf 265 PQVIALHRSQAQSSV 13 214 PPPIQVSALHHSPPL 96 position is specified, the length 222j LHHSPPLVQATALHH) of peptide is 15 amino acids, - PPLVQATALHHSPPS |g and the end position for each I Table XLIX-109P1 D4v. 3 peptide is the start position plus DRB1 1101-15-mers F233 ln6 fourteen Each peptide is a portion of SEQ 235 HHSPPSAQASALCYS 16 ID NO : 7 ; each start position is 240 SAQASALCYSPPLAQ 16 108 EGDGNSDPESTFIPG 26 specified, the length of peptide is H| LCYSPPLAQAAAISH 16 87 GLPLGYPQEEYFDRA 24 amino acids, and the end position for each peptide is the 249 SPPLAQAAAISHSSP 16 318 DDSIKVIPLTTFTPR 20 start position plus fourteen 258 ISHSSPLPQVIALHR 16 33 EIWIHPQPQRKSEGK 19 268 IALHRSQAQSSVSLQ 16 117 STFIPGLKKAAEITV 19 13 RPPMKEVVRSCTPMK 26 292 LCSVDQGVQGSATSQ 16 13 RPPMKEVVRSCTPMK 18 264 LPQVIALNRSQAQSS 26 300 QGSATSQFYTMSERL 16 57 TFHLPEGSQESSSDG 18 289 ADGLCSVDQGVQGSA 26 323) VIPLTTFTPRQQARP |S E|DGGLGDHDAGSLTST|S m| VTTFEVPVSVHTRPP | 7 PVSVHTRPPMKEVVR 15 616 ESTFIPGLKKAAEIT 18 153 DACWMPASLDHSSSS 22 fla RPPMKEVVRSCTPMK 15 128 EITVQPTVEEASDNC 18 5 EVPVSVHTRPPMKEV 20 ri MKEVVRSCTPMKEST |S Mj|DQGVQGSATSQFYTM|S E| MKEWRSCTPMKEST 47 KVAGKSQRRVTFHLP 15 31 TMEIWIHPQPQRKSE 1 23 CTPMKESTTMEIWIH 20 56 VTFHLPEGSQESSSD 95 45 EGKVAGKSQRRVTFH 17 33 EIWIHPQPQRKSEGK 20 72 GLGDHDAGSLTSTSH 15 47 KVAGKSQRRVTFHLP 17 57 TFHLPEGSQESSSDG 20 mil DHDAGSLTSTSHGLP 15 86 HGLPLGYPQEEYFDR 17 120 IPGLKKAAEITVQPT 20 85 SHGLPLGYPQEEYFD 1 104 SNRTEGDGNSDPEST 17 132 QPTVEEASDNCTQEC 20 Table TableXLIX-109PlD4v. 3 Table XLIX-109P1 D4v. 3 Each peptide is a DRB1 1101-15-mers DRB1 1101-15-mers portion of SEQ ID Each peptide is a portion of SEQ Each peptide is a portion of SEQ N0 : 9 ; each start ID NO : 7 ; each start position is ID NO : 7 ; each start position is position is specified, the length of peptide is specified, the length of peptide is specified, the 15 amino acids, and the end 15 amino acids, and the end length of peptide is position for each peptide is the position for each peptide is the 9 amino acids, and start position plus fourteen start position plus fourteen | the end posibon for I | each peptide is the start position plus 1581) PASLDHSSSSQAQAS 20 53 QRRVTFHLPEGSQES 4. 177 SPPLSQASTQHHSPR 20 70 DGGLGDHDAGSLTST 14 Fl-9311 TQTIALCHSPPVTQT 119 F7811 AGSLTSTSHGLPLGY 14 P2 F216] 1 PIQVSALHHSPPLVQ 1201 265 PQVIALHRSQAQSSV 20 1 AAEITVQP 283 QGWVQGADGLCSVDQ 20 128 EITVQPTVEEASDNC 14 QPQSQRRVT 292 LCSVDQGVQGSATSQ 20 1 4 QECLIYGHSDACWMP 14 320 SIKVIPLTTFTPRQQ 20 954 ACWMPASLDHSSSSQ l4 Table XXIII _ 1109P1D4V. 4-A0201 I | VIPLTTFTPRQQARP |E E ASALCHSPPLSQAST 14 l 9-mers 56 VTFHLPEGSQESSSD 18 195 TIALCHSPPVTQTIA 14 Each peptide is a F7211 GLGDHDAGSLTSTSH 18 205 TQTIALCHSPPPIQV 14 portion of SEQ ID 155 CWMPASLDHSSSSQA 18 207 TiALCHSPPPIQVSA 94 N0 : 9 ; each start position is specified, 156 WMPASLDHSSSSQAQ 18 214 PPPIQVSALHHSPPL 14 the length of peptide 174 LCHSPPLSQASTQHH 18 219 VSALHHSPPLVQATA 14 is 9 amino acids, === ==-N r= and the end position 186 QHHSPRVTQTIALCH 18 225 SPPLVQATALHHSPP 14 and the end position 0 0 for each peptide is F LCHSPPVTQTIALCH 18 226 PPLVQATALHHSPPS 14 the start position fez LHHSPPLVQATALHH 18 231 ATALHHSPPSAQASA 14 plus eight 246 LCYSPPLAQAAAISH 18 243 ASALCYSPPLAQAAA 14 AAAISHSSPLP I SPPLAQ il (SHSSPLPQVIALHR 18 255 AAAISHSSPLPQVIA 14 0 PQPQS_QRRV 7 263 PLPQVIALHRSQAQS 18 261 SSPLPQVIALHRSQA 14 IWIHPCPQS 6 269 ALHRSQAQSSVSLQQ 18 267 VIALHRSQAQSSVSL 14 275 AQSSVSLQQGWVQGA 18 276 QSSVSLQQGWVQGAD 14 Table XXIV 0 109P1 D4v. 4- 286 VQGADGLCSVDQGVQ 18 278 SVSLQQGWVQGADGL 14 A0203 312 ERLHPSDDSIKVIPL 18 296 DQGVQGSATSQFYTM 14 9-mers S| QEEYFDRATPSNRTE |E iRil SERLHPSDDSIKVIP liS 32 1 MEIWIHPQPQRKSEG 19 HI DDSIKVIPLTTFT=PR 89 PLGYPQEEYFDRATP 16 Found. PLGYPQEEYFDRATP 16 '' 95 EEYFDRATPSNRTEG 16 Table XXII 9 09P1 D4v. 4-A1 Table XXV 116 ESTFIPGLKKAAEiT < m Ei| CLIYGHSDACWMPAS |g 245 ALCYSPPLAQAAAIS 16 305 SQFYTMSERLHPSDD 16 | EGKVAGKSQRRVTFH | | TFEVPVSVHTRPPMK @ fi STTMEIWIHPQPQRK 14 E| TME, WIHPQPQRKSE 1S Each peptide is a Table XXVIII Table XXXI portion of SEQ ID 109P1 D4v. 4-B08 109P1 D4v. 4 NO : 9 ; each start 9-mers B2709-9-mers position Is specified, position is specified, Each peptide is a Each peptide is a the length of peptide is 9 amino portion of SEQ ID portion of SEQ ID acids, and the end N, 2 : 9 ; each start NO : 9 ; each start position is specified, position is position for each the length of peptide specified, the peptide is the start is 9 amino acids, length of peptide is position plus eight and the end position 9 amino acids, and for each peptide is the end position for 15 the start position each peptide is the plus eight start position plus 14 1 1 eight i PQSQRRVTF i 5 I 11 QSQRRVTFH PQPQSQRRV S SS HPQPQSQRR. 7. Swg W| IWIHPQPQS |E Table XXVI 109P1D4V. 4-A26 Table XXIX 9-mers 11 109P1D4v. 4 Table XXXII B1510-9-mers 109P1 D4v. 4 Each peptide is a 84402-9-mers portion of SEQ ID Each peptide is a NO : 9 ; each start portion of SEQ ID Each peptide is a position is NO : 9 ; each start portion of SEQ ID specified, the position is specified, NO : 9 ; each start length of peptide is the length of position is specified, 9 amino acids, and peptide is 9 amino the length of the end position acids, and the end peptide is 9 amino for each peptide is position for each acids, and the end the start position peptide is the start position for each plus eight position plus eight peptide is the start position plus eight fflj|PQSQRRVTF| {HPQPQSQRt |WIHPQPQSQ| | PQSQRRVTFX jPQSQRRVTF|S| ''SpOPQk x,, 1 121 IWIHPQPQS 1il '1 jl IWIHPQPQS 1E 1'""'t Table XXX 109P1D4v. 4-B2705 Table XXXIII Table XXVII 9-mers 109PID4v. 4-B5lOl 109P1 D4v. 4-B0702 9-mers 9-mers Each peptide is a portion of SEQ ID Each peptide is a Each peptide is a NO : 9 ; each start portion of SEQ ID portion of SEQ ID position is specified, NO : 9 ; each start NO : 9 ; each start the length of peptide position is specified, position is specified, is 9 amino acids, the length of peptide the length of peptide and the end position is 9 amino acids, is 9 amino acids, for each peptide is and the end position and the end position the start position for each peptide is for each peptide is plus eight the start position the start position plus eight plus eight' 1 IHPQPQSQR t ln8 14 12 |E|QPQSQRRVTf HPQPQSQRRF QPQSQRRVT| INIHPQPQSQRRR PQSQRRVTF ! PQPQSQRRVlg| HPQPQSQRRfM 7) PQSQRRVTF =,. -- |M| PQSQRRVTF l QSQRRVTFH X HPQPQSQRR|g TPQSQRRVTF QSQRRVTFH ="=Ji Table XXXIV Each peptide is a Table 109P1 D4v. 4-A1 portion of SEQ ID XL- 10-mers NO : 9 ; each start 109P1 D4 Each peptide is a position is specified, v. 4-B08- portion of SEQ ID l the length of peptide 1 10-mers NO : 9 ; each start is 10 amino acids, and the nd position position is specified, and the end position the iength ofpepMe.. ",. is 10 amino acids, and the end position nine Found. for each peptide is I- the start position piwlh WIHPQPQSQR 21 Table XLI plus nine I _. _ 1 O9P1 D4v4- il 7 IQPQSQRRVTF 15 B15 iO ELEIWIHPQPQS |S 10-mers W|W ! HPQPQSQR|S EIHPQPQS-QRRVIH Table XXXVIII No Results M QSQRRVTFHLj) 4 109P1D4v. 4-A26 Found. 6 PgPQSQRRVT 2 10-mers Each peptide is a Table XLII Table XXXV portion of SEQ ID 109P1 D4v. 4- N0 : 9 ; each start 10-mD4v, 4-A0201 position is specified, I 705 10-mers 10-mers the length of peptide Each peptide is a is 10 amino acids, portion of SEQ ID NO : and the end position 9 ; each start position for each peptide is Found. is specified, the length the start position plus of peptide is 10 amino nine acids, and the end Table XLIII position for each 109P1 D4v. 4- peptide is the start El EIWIHPQPQS 15 g7pg 10-mers position plus nine ne QPQSQRRVTF 10-mers |QSQRRVTFHL|S , EIWIHPQPQSQR 7] 11 Found. 1 |g| QSQRRVTFHL 10 Table XXXIX 1 EIWIHPQPQS 7 109P1D4v. 4-B0702 Table XLIV L=======J= 109P1D4v. 4-B4402 |2| IWIHPQPQSQ ! 10-mers | 10-me ; s Each peptide is a = portion of SEQ ID NO : Each peptide is a Table XXXVI 9 ; each start position portion of SEQ ID 109P1D4v. 4- is specified, the length NO : 9 ; each start A0203 of peptide is 10 amino position is specified, 10-mers acids, and the end the length of peptide position for each is 10 amino acids, peptide is the start and the end position position plus nine for each peptide is Found. the start position plus nine IQPQSQRRVTF 19 nine 109P1 D4v. 4 HPQPQSQRRVE QPQSQRRVTFISI || A3-10-mers | QSQRRVTFHLZ QSQRRVTFHL|S| Table XLV j) Each peptide is a 109P1D4v. 4- 4 TMEIWIHPQPQSQRR 20 portion of SEQ ID B5101 NO : 11 ; each start 10-mers position is specified, ml STTMEIWIHPQPQSQ |E the length of No Results 6 EIWIHPQPQSQRRVT 14 pptide is 9 amino acids, and the end Found. ESTTMEiWIHPQPQS 1 position for each HITTMEIWIHPQP-QSQR 12 peptide is the start r Tt. t v. . < ! nnr. =1 ===i= poshon pius oght Table XLVt-109P1D4v. 4 WiHPQPQSQRRVTFH ! tl2 == DR1 0109-15-mers Each peptide is a portion of SEQ ID NO : 9 ; each start position is specified, the length Table XLIX-109P1 D4v. 4 of peptide 15aminoacids, I DRB1 1101-15-mers and the end position for each Table XXIV peptide is the start position SEQ D NO : 9'each start ° D'S SEQ ID N0 : 9 ; each start plus fourteen position is specified, the A0203-9- length of peptide is 15 amino mers m| STTMEIWIHPQPQSQ |S acids, and the end position for each peptide is the start W| TMEIWIHPQPQSQRR |S position plus fourteen n5 IMEIWIH 9 13 PQSQRRVTFHLPEGS 16 2 STTMEIWIHPQPQSQ 20 Table XXV 8 WIHPQPQSQRRVTFH 15 13 PQSQRRVTFHLPEGS 13 109P1D4v. 5-A3 - 6 i EIWIHPQPQSQRRVT IER3 W|TMEIWIHPQPQSQRR |S 9-mers 10 HPQPQSQRRVTFHLP 14 5 MEIWlHPQPQSQRRV 10 Each peptide is a 12 QPQSQRRVTFHLPEG 14 9 IHPQPQSQRRVTFHL 10 Portion of SEQ ID R NO : 11 ; each start gj TTMEIWIHPQPQSQR 12 position is specified, Table XXII the length of Table XLVII-109P1 D4v. 4 109P1 D4v. 5-A1 peptide is 9 amino DRB10301-15-mers I 9-mers acids, and the end. position for each Each peptide is a portion of Each peptide is a peptide is the start SEQ ID NO : 9 ; each start portion of SEQ ! D position pius eight position is specified, the length NO NO 11 ; each start of peptide is 15 amino acids, position is specified, and the end position for each the length of peptide is the start position peptide is 9 amino plus fourteen acids, and the end position for each peptide is the start Table XXVI 6 EIWIHPQPQSQRRVT 18 position plus eight 109P1D4v. 5-A26 n4 ITMEIWI 9 9-mers IHPQPQ 1 Each peptide is a position of SEQ ID STTMEIWIHPQPQSQ {l|VSVHTRPSQt NO : l l ; each start position is specified, Table XLVIIf-109P1 D4v. 4 the length of DRB1 0401-15-mers peptide is 9 amino Table YJCIII acids, and the end Each peptide is a portion of 109Pl D4v. 5 position for each SEQ ID NO : 9 ; each start A0201-9-mers peptide is the start position is specified, the position plus eight length of peptide is 15 amino acids, and the end position for each peptide is the start 3SVHTRPSQRJ13 position plus fourteen N91 Table XXVI Each peptide is a 109P1D4v. 5-A26 portion of SEQ ID Table XXXII 9-mers NO : 11 ; each start 109P1D4v. 5 Each peptide is a position is specified, B4402-9-mers portion of SEQ ID the length of peptide is 9 amino Ech pepfide is a NO : 11 ; each start Snd nSEQ position is specified,-tifor 0 : 11 ; each start ihe lenglh of poition is specifed, peptide is 9 amino pepCide is th st : position plus eight the length o acids, and the end peptide is 9 amino position for each acids, and the end peptide is the start position for each position plus eight RPSQRRVTF 2 PeP is the start position plus eight RpsoRfv E ! S ! ! E [ EFRP-SQ-RRVTFIE9 HITRPSQR-RV-Tlg NFR-P S-Q-R R-V-T-F 3 SVNTRPSQR 5 Table XXVII Table XXX Table XXVii ogp p g,... 109P1D4v. 5 109P1D4v. 5 Table XXXIII W|SVHTRPSQR|E LM LX Each peptide is a B5101-9-mers Each peptide is a portion of SEQ ID portion of SEQ ID N0 : 11 ; each start Each peptide is a NO : 11 ; each start position is specified, I portion of SEQ ID position is specified, the length of NO : 11 ; each start the length of peptide is 9 amino position is specified, peptide is 9 amino acids, and the end the length of acids, and the end position for each peptide is 9 amino position for each acids, and the end peptide is the start peptide is the start position plus eight position for each I-Iposition plus eight I position plus eight 7 RPSQRRVTF 22 PSQRRVTF 18 |EL TRPSQRRV|2 |VHTRPSQRR| |i| RPSQRRVTF | S Eff-9 H F,-21 EF II Table XXVIII || W|TRPSQRRVT|E |ELTRPSQRRVT|F 109PID4v. 5 608-9-mers Table XXXIV Each peptide is a Table XXXI 109P1 D4v. 5-A1 portion of SEQ ID 109P1 D4v. 5 10-mers NO : 11 ; each start B2709-9-mers Each peptide is a position is specified, Each peptide is a portion of SEQ D the length of portion of SEQ ID NO : 11 ; each start peptide is 9 amino N0 : 11 ; each start position is specified, acids, and the end the length of peptide position for each position is 10 amino acids, phe le gth of is 10 amino acids, peptide is the start and the end osition position plus eight peptide is 9 amino P acids, and the end for each peptide is position for each the start position plus 7 JRPSQRRVTF 2 ? peptide is the start nine |ELSVHTRPSQRT positionpluseight t H-RPSQßRVT|gt II Table XXIX 11 |@lRPSQRRVTFt VSVHTRPSQR|E| 109P1D4v. 5 6 TRPSQRRVT) B1510-9-mers 5 HTRPSQRRV fl0 Table XXXV Each peptide is a 109P1D4v. 5 portion of SEQ ID Table XLII A0201-1 O-mers NO : 11 ; each start 109P1D4v. 5 Each peptide is a position is specified, B2705-10- portion of SEQ ID the length of peptide mers is 90 amino cids, f-1 NO : 11 ; each start is 10 amino acids, position is specified, and the end position and the end position I is 10 amino acids, nixe and the end position for each peptide is Table XLIII the start position plus HIPVSVHTRPSQ 11 109Pl D4v. 5 nine I r B2709-10-I nine B2709-1 0- mers 7VHTRPSQRRVTF 11 VHTRPSQRRVtflO RPSQRRVTF"== 6 HTRPSQRRVT 10 SQRRVTFHLE L M| PSQRRVTFHL| M| PSQRRVTFHL |S Found. 3 VSVHTRPSQRR6 Table XLIV 4 SVHTRPSQRR 6 Table XLIV !-----) TaMeXXXiX inmorQ Table 109P1 D4v. 5 10-mers B0702-10-mers Each peptide is a 1 Q9P1 D4v. 5 109PID4v. 5 portion of SEQ ID mers portion of SEQ ID N0 : 11 ; each start position is specified, Nô : 11 ; each start the length of peptide position is specified, is 10 amino acids, No Results the length of peptide and the end position Found. is 10 amino acids, for each peptide is and the end position the start position plus Table XXXVII for each peptide is the start position plus nine I 0-mers nine 10-mers Each peptide is a 11 l l portion of SEQ ID 8 RPSQRRVTFH 16 9 PSQRRVTFHL 12 NO : 11 ; each start IVPVSVHTRPSIM position is specified, Table XLV the length of peptide 109P1 D4v. 5 is 10 amino acids, 9 PSQRRVTFHL 9 9 B5101-10- and the end position 7 TRPSQRRVTF 9 mers for each peptide is the start position plus nine Table XL 109P1 D4v. 5 Found. B08-10- SVH_TRPSQRR 15 mers 2 PVSVHTRPSQ 13 TabIeXLVI-109P1D4v. 5 0 0 DRB1 0101-15-mers EITRPSQRRVTFI 13 Each peptide is a portion of F, 11 SEQ ID NO : 11 ; each start position is specified, the Table XLI lengt of peptide is 15 amino 109P1D4v. 5 acids, and the end position for Table XXXVIII each peptide is the start 109P1D4v. 5-A26-10- g. g'position pius fourteen mers II mers 1} l-1 No Results 4 FEVPVSVHTRPSQRR 22 Found. 3 TFEVPVSVHTRPSQR 17 Table XLVI-109P9 D4v. 5 Table XXIII DRB1 0101-15-mers Table XLIX-109P1D4v. 5 109P1D4v. 6 Each peptide is a portion of DRB1 1101-15-mers C'terminal-A0201 SEQ ID NO : 11 ; each start Each peptide is a portion of 9-mers position is specified, the SEQ ID NO : 11 ; each start Each peptide is a length of peptide is 15 amino position is specified, the portion of SEQ ID acids, and the end position for length of peptide is 15 amino NO : 13 ; each start each peptide is the start acids, and the end position for position is position plus fourteen each peptide is the start specified, the position plus fourteen length of peptide is 9 amino acids, and in the end position for 3 RPSQRRVTFHLPEGS 16 TFEVPVSVHTRPSQR 25 each peptide is the |PVSVHTRPSQRRVTFlE W|EVPVSVHTRPSQRRV|S I startpositionplus H|VHTRPSQRRVTFHLP |E | VTTFEVPVSVHTRPS |g I 12 TRPSQRRVTFHLPEG 14 0 FEVPVSVHTRPSQRR 13 3 SVHTRPTDS 13 RPSQRRVTFHLPEGS 13 4 VHTRPTDSR 5 Table XLVIi-109P1 D4v. 5 I DRB10301-15-mers Table XXII Each peptide is a portion of 109P1D4v. 6 Table XXIV SEQ ID NO : 11 ; each start C'terminal-Al 109P1D4v. 6 position is specified, the 9-mers C'terminal- length of peptide is 15 amino Each peptide is a A0203 acids, and the end position for portion of SEQ ID 9-mers each peptide is the start NO : 13 ; each start position plus fourteen position is No Results specified, the Found. length of peptide is 0 li 9 amino acids, and 10 VHTRPSQRRVTFHLP 16 the end position for Table XXV 7 PVSVHTRPSQRRVTF 12 each peptide is the 109P1 D4v. 6 start position plus C'terminal-A3 3 TFEVPVSVHTRPSQR 10 eight 9-mers 1-1 1 Each peptide is a 11 8 VSVHTRPSQRRVTFH 8 5 HTRPTDSRT 10 portion of SEQ ID } n h start l' 9 SVHTRPSQRRVTFHL 8 2 VSVHTRPTD 6 Npositionhs tart 12 TRPSQRRVTFHLPEG specified, the 111 r S 11 Table XXlll length of peptide is Table XLVNI-109P9D4v. 5 109P1D4v. 6 9 amino acids, and DRB10401-15-mers C'terminal-A0201 the end position for 9-mers each peptide is the Each peptide is a portion of start position plus SEQ ID NO : 11 ; each start Each peptide is a eight position is specified, the portion of SEQ ID length of peptide is 15 amino NO : 13 ; each start acids, and the end position position is 3) SVHTRPTDS ! 15 for each peptide is the start specified, the 1 PVS_VHTRPT 10 position plus fourteen Length of peptide is 9 amino acids, and 4 VHTRPTDSR 9 the end position for | HT_PTDSRT|g| lEi VTTFEVPVSVHTRPS {each peptide is the || INIEVPVSVHTRPSQRRVX startpositionplus 11 eight Table XXVI FEVPVSVHTRPSQRR 18 109P1D4v. 6 3 TFEVPVSVHTRPSQR 4 C'terminal 8 VSVHTRPSQRRVTFH "" , HISVHTRPSQRRVTFHL Each peptide is a Table XXXI portion of SEQ ID Table XXIX 109P1D4v. 6 NO : 13 ; each start 109P9 D4v. 6 C'terminal-B2709 position is C'terminal 9-mers specified, the B1510-9-mers Each peptide is a length of peptide is 9 amino acids, and portion ofi SEQ ID NO : 13 ; each start Xde'X NO : 13 ; each sM Points each peptide is the position i specified, the str position plus specified, the length of peptide is 9 mino acid length off peptide in 9 amino acids, and and the end |SVHTRPTDS|g the end position for position for each - r-each peptide is the peptide is the start start position plus position plus eight 5 HTRPTDSRT 10 eighl |VSVHTRPTD| l l l|VSVHTRPTD| l W|VHTRPTDSR|E W|HTRPTDSRT| Table XXVII 31 PVSVHTRPT |E |VHTRPTDSR|0 -) nQpinj. \/R =n r= LJ ! ! LJ 109P1D4v. 6 HTRPTDSRT 4 C'terminal-B0702 9-mers Table XXXI I Each peptide is a Table XXX 109P1D4v. 6 portion of SEQ ID 109P1 D4v. 6 C'terminal-B4402 NO : 13 ; each start C'terminal-B2705 9-mers position is 9-mers Each peptide is a specified, the Each peptide is a portion of SEQ ID length of peptide is portion of SEQ ID NO : 13 ; each start 9 amino acids, and NO : 13 ; each start position is the end position for position is specified, the each peptide is the specified, the length of peptide start position plus length of peptide is is 9 amino acids, eight 9 amino acids, and and the end the end position for position for each FP PVSVHTRPT 10 each peptide is the peptide is the start start position plus position plus eight HTRPTDSRT 9 eight 4J) VHTRPTDSR Hm 3 SVHTRPTDS 4 VHTRPTDSR 12 1 pVSVHTRPT 3 Table XXViII HTRPTDSRT 5 5HTRPTDSRT 3 109P1 D4v. 6 C'terminal-BOB 9-mers Table XXXI 4 VHTRPTDSR Each peptide is a 109P1 D4v. 6 ? C'terminai-B2709, portion of SEQ ID C'terminal-B2709 NO : 13 ; each start 9-mers-Table XXXI I I position is Each peptide is a 109Pl D4v. 6 specified, the portion of SEQ ID C'terminal-B5101 length of peptide is NO : 13 ; each start 9-mers 9 amino acids, and position is the end position for specified, the each peptide is the length of peptide start position plus is 9 amino acids, eight and the end position for each peptide is the start FS SVHTRPTDS 10 position plus eight iilHTRPTDSRT Each peptide is a Table Each peptide is a portion of SEQ ID XXXV) portion of SEQ ID NO : 13 ; each start 109P1D4v. 6 NO : 13 ; each start position is C'terminal-position is specified, specified, the A0203 the length of peptide length of peptide 10-mers is 10 amino acids, is 9 amino acids, and the end position and the end for each peptide is position for each | No Results the start position plus peptide is the start Found. nine position plus eight l I Table XXXVII W|VPVSVHTRPT|S 2) VSVHTRPTD ! f4 3 VHTRPTDSRT) k\/nTRpTnc ; ! R"term) nai-A3 ! L) t--"-' ! 3 VHTRPTDS 10-mers 5 HTRPTDSRT Each peptide is a Table portion of SEQ ID XL- Table XXXIV NO : 13 ; each start 109P1D4 109P1 D4v. 6 position is specified, v. 6-C' the length of peptide terminal- 10-mers is 10 amino acids, 10-mers and the end position 10-mers Each peptide is a for each peptide is portion of SEQ ID the start position plus NO : 13 ; each start nine position is specified, Results the length of Found. peptide is 10 amino W|SVHTREDSR|M acids, and the end PTDSR position for each 11 XLI-11 peptide is the start 109P1 D4 position plus nine Table XXXVIII v. 6-C' 109P1 D4v. 6 terminal 3 VSVHTRPTDS 5 C'terminal-A26 B1510- 0 10-mers 10-mers H|S_HTRPTDSR|l | Each peptide is a portion of SEQ ID Table XXXV NO : 13 ; each start No 109P1D4v. 6 position is specified, Results C'terminal-A0201 the length of peptide 10-mers is 10 amino acids, and the end position Table Each peptide is a for each peptide is XLII- portion of SEQ ID the start position plus 109P1 D4 NO : 13 ; each start nine v. 6-C' position is specified, terminal the length of || peptide is 10 amino} SVHTRPTDSRE acids, and the end 10-mers position for each 0 peptide is the start No peptide is the start , No position plus nine Table XXXIX Results 109P1D4v. 6 Found. C'terminal-B0702 0 10-mers |S|VPVSVHTRPTX 2 PVSVHTRPTD 4 109P1D4v. 6 00 C'terminal- 5 VHTRPTDSRT 4 B2709 10-mers rm No Results Each peptide is a portion of Each peptide is a Found. SEQ ID N0 : 13 ; each start portion of SEQ ID position is specified, the NO : 13 ; each start Table XLIV length of peptide is 15 amino position is specified, 109PID4v. 6 ac s, and the end position the length of peptide C'terminal-64402 for each peptide is the start is 9 amino acids, I 0-mers position plus fourteen and the end position for each peptide is Each peptide is a the start position portion of SEQ ID 5 EVPVSVHTRPTDSRT J16 plus eight NO : 13 ; each start 3 TFEVPVSVHTRPTDSJ10 1 VTTFEVPVSVHTRPT 9 6 NSDIS VVR 15 thé length of eds peptide is 10 amino I E|HKCLLSGTY|S acids, and the end Table XLVIII-109P1D4v. 6 1 MTVGFNSDI position for each C'terminal-DRB1 0401 1-11 8 peptide is the start 15-mers 17 TTNCHKCLL E position piu nié Each peptide is a portion of S|TNCHKCLLS|E SEQ ID NO : 13 ; each start 91PVSVHTRPTD13 position is specified, the length of peptide is 15 amino IMPUR H p acids, and the end position,,,"' N. IVPVSVHTRPT19 for each peptide is the start 9-mers position plus fourteen Table XLV Each peptide is a ,''-,.,.-portion of SEQ iD 109PID4v. 6 IVTTFEVPVSVHTRPT 22 portion of SEQ ID C'terminal-0 NO : 13 ; each start B5101 PIFEVPVSVHTR position is specified, the length of peptide 90-mers 3 TFEVPVSVHTRPTDS 94 is 9 amino acids, 5J EVPVSVHTRPTDSRT) 14 and the end position No Results for each peptide is Found, Table XLIX-109P9 D4v. 6 the start position C'terminal-DRB1 1101 plus eight Table XLVI-I 09PI D4v. 6 15-mers C'terminal-DRBI 0101 Each peptide is a portion of SDISSYVRV 15-mers SEQ ID NO : 13 ; each start 41 Each peptide is a portion of position is specified, the s CLLSGTYIF 17 SEQ ID NO : 13 ; each start length of peptide is 15 amino 00 position is specified, the acids, and the end position MTVGFNSDI 15 length of peptide is 15 amino for each peptide is the start 17 TTNCHKCLL 15 acids, and the end position for each peptide is the start 10 SSWRVNTT 13 position plus fourteen 3 TFEVPVSVHTRPTDS 25 FNSDISSW 92 I EVPVSVHTRPTDSRT 15 16 NTTNCHKCL 12 3 tTFEVPVSVHTRPTDS 17 VTTFEVPVSVHTRPT 13-S-D'SSWRVN 11 1 VTTFEVPVSVHTRPT 16 22 KCLLSGTYI 11 |W|FEVPVSVHTRPTDSR} Table XXII |S|EVPVSVHTRPTDSRTT lO9PlD4v. 6} Table XXIV N'terminal-A1 109P1D4v. 6 9-mers N'terminal- TabIeXLViI-109P1D4v. 6 A0203 C'terminal-DRB1 0301 9-mers 15-mers No Results Found. Table XXV Table XXVII Table XXV Table XXVII 109P1D4v. 6 109P1D4v. 6 Table XXIX N'terminal N'terminal-B0702 1 109P1D4v. 6 A3-9-mers 9-mers N'terminal-B1510 Each peptide is a Each peptide is a 9-mers portion of SEQ ID portion of SEQ ID Each peptide is a NO : 13 ; each start NO : 13 ; each start portion of SEQ ID position is specified, position is specified, NO : 13 ; each start the length of peptide the length of peptide position is specified, is 9 amino acids, and is 9 amino acids, the length of peptide the end position for and the end position is 9 amino acids, each peptide is the for each peptide is and the end position start position plus the start position for each peptide is eight plus eight the start position plus eight 14 RVNTTNCHK 24 9 ISSWRVNT 12 11 SVVRVNTTN 20 16 NTTNCHKCL 10 17 TTNCHKGLL 12 23 CLLSGTYIF 18 17 TTNCHKCLL 10 16 NTTNCHKCL 10 12 WR_VNTTNC 14 FNSDISSVV 20 CHKCLLSGT 10 DISSWRV FISSVVRVNT] n6 DISSVVRVN 13 22 KCLLSGTYI 9 23 CLLSGTYIF 7 21 91 KCLLSGTY11 lfl S|SSWRVNTT|E Table XXVI 23 CLLSGTYIF 7 Table XXX 109P1 D4v. 6 109P1 D4v. 6 N'terminal-A26 0 GFNSDISSV 6 N'terminal-B2705 9-mers 20 GHKCLLSGT 6 9-mers Each peptide is a Each peptide is a portion of SEQ ID Table XXVIII portion of SEQ ID NO : 13 ; each start 109P1D4v 6 NO : 13 ; each start position is specified, N'terminal-B08 position is specified, P P N terminal-B08 the length of peptide 9-mers the length of peptide is 9 amino acids, and is 9 amino acids, and the end position for Each peptide is a the end position for each peptide is the portion of SEQ ID each peptide is the start position plus NO : 13 ; each start start position pius eight position is specified, eight the length of peptide is 9 amino acids, and 8 DlSSVVRVN 97 the end position for 13 VRVNTTNCH 20 16 NTTNCHKCL 97 each peptide is the 14 RVNTTNCHK 15 starf position plus |TTNCHKCLL|S ll eight 23 CLLSGTYIF 15 11 SVVRVNTTN ]6 6 NSDISSVVR 14 Fil MTVGFNSDI 13 10 SSWRVNTT 12 22 KCLLSGTYI 14 RHK HKCLLSGTY) (13 23 CLLSGTYiF t JHKCLLSGT EFTVGFNSDISIE 9 IR 12 VVRVNTTNG 11 17 TTNCHKGLL 10 17 TTNCNKCLL 11 7 SDISSVVRV 10 18 TNCHKCLLS 10 16 NTTNCHICL 10 10 SSVVRVNTT 10 20 CHKCLLSGT 10 14 RVNTTNCHK 10 12 WRVNTTNC 8 Table XXXI 109PI D4v. 6 00 000 N'terminal-82709 22 KCLLSGTYI 7 9-mers Each peptide is a Each peptide is a portion of SEQ ID portion of SEQ ID | VGFNSDISSV | ji18 NO : 13 ; each start NO : 13 ; each start position is specified, position is specified, ecified, the length of peptide the length of peptide 23 CLLSGTYIFA 116 is 9 amino acids, and is 9 amino acids, the end position for and the end position each peptide is the for each peptide i5 B| ISSWRVNTT |g start position pius the start position H|NTTNCHKCLL|g eight plus eight W| GFNSD ! SSW |S E| GFNSDISSV |F E| KCLLSGTYI | HwS SDISSWRV 13 MT1/GFNSDI 13 ijl I<CLLSGTYI 12 FNSDISSVV 13 2n3 CLLSGTYIF lit ; SDfSSWRV 13 109P1D4v 6 13 VRVNTTNCH 11 Q8 DISSVVRVN 12 N'terminal-A0203 ln6 1 0-mers Each peptide is a portion of SEQ ID 1 MTVGFNSDij) 9 16j) NTTNCHKCL)) 8 NO : 13 ; each start position is specified, the length of peptide is 10 amino acids, Table XXXII Table XXXIV and the end position 109P1 D4v. 6 109P1 D4v. 6 for each peptide is N'terminal N'terminal-A1 the start position B4402-9-mers 10-mers plus nine Each peptide is a Each peptide is a portion of SEQ ID portion of SEQ ID NO : 23 CLLSGTYIFA 10 NO : 13 ; each start 13 ; each start position position is specified, is specified, the length the length of peptide of peptide is 10 amino Table XXXVII is 9 amino acids, acids, and the end 109P1 D4v. 6 and the end position position for each N'terminal-A3 I for each peptide is 11 peptide is the start 11 11 1 O-mers li for each peptide is peptide is the start 10-mers the start position position plus nine plus eight Each peptide is a portion of SEQ ID NO : F151 13 ; each start position 16 NTTNCHKCL 14 20 CH_KCLLSGTY 15 is specified, the length 21 HKCLLSGTY 12 of peptide is 10 amino 00 17 TTNCHKCLLS 14 acids, and the end 23 CLLSGTYIF 92 16 NTTNCHKCLL 8 position for each 17 TTNCHKCLL 11 pepfide is the start === L= pos ! t) on pius nfne 22 KCLLSGTYI 11 Table XXXV Position plus nine N'terminal-A0201 FA F17 SVVRV_TNC} 10-mers 11 SVVRVNTTNC 15 Each peptide is a 14 RVNTTNCHKC 14 109P1 D4v. 6-- N'terminal-85101 porfian of SEQ ID N0 ; 5 FNSDISSWR 13 9-mers 13 ; each start position is specified, the length E ln3 of peptide is 10 amino TVGFNSD1SS 12 acids, and the end 2nO 12 position for each 11 peptide is the start 23 CLLSGTYIFA 12 position plus nine 9'Ri VRVNTTNCHK 11 Table XXXVII Each peptide is a 109P1D4v. 6 portion of SEQ D NO : No N'terminal-A3 13 ; each start position Results 10-mers is specified, the length Found. Each peptide is a of peptide is 10 amino portion of SEQ ID NO : acids, and the end position for each Table is speciM, the length Ps he start XLitf- of peptide is 10 amino position plus nine _j 109PI D4 of peptide is 10 amino v. 6 N' acids, and the end v. 6 N' position for each terminal- peptide is the start B2709 position plus nine 11-01 1 0-mers Fill ISSVVRVNTTIE E| KCLLSGTYIF |S 15 VNTTNCHKCL S No 16 NTTNCHI (CLL 10 Results Found. Table XXXVIII 22 KCLLSGTYIF 8 109P1 D4v. 6 4l S j GFNSDISSW |E N'terminal-A26 g NCNKCLLSGT 7 v. 6 N'terminal 10-merls Each peptide is a 4402-10-mers Mach peptide is a portion of SEQ ID N0 : 23 CLLSGTYIFA 7 Each peptide is a 13 ; each start position portion of SEQ ID N0 : 1 13, each start position I iml 17 llportion of SEQ ID NO : is specified, the length GFNSDISSV 6 13 ; each start position of peptide is 10 amino is specified, the length acids, and the end Table of peptide is 10 amino position for each XL-acids, and the end position for each peptide is the start 109P1 D4 position plus nine v. 6 N'peptide is the start terminal-position plus nine B08 I 16 NTTNCHKCLL 17 1Q-mers 11 SVVRVNTTNC 15 22 KCLLSGTYIF 14 L--1 15 VNTTNCHKCL 13 T TVGFNSDISS 13 No 8 DISSVVRVNT 13 Results 16 NTTNCHKCLL 13 Table ==== CLLSG [SDiSSVVRVNl 0° XLI- 3nl VGFNSDISSV 10 109P1D4 Tabie 10 v. 6 N'XLV- 12 WRVNTTNCH 10 81510 ! 109P1D4 17 TTNCHKCLLS 10 10-mers v. 6 N' terminal 15 VNTTNCHKCL 9 L, B5101- Nô 10-mers Results -- Table XXXIX Results 109P 1 D4v. 6 No || lO9PlD4v. ó || li Found. q 11 No 11 N'terminal-80702 Results 10-mers Table Found. XLII- ll1 09P1 D4E 109P1 D4 Table XLVI- 09P1 a4v. 6 v. 6 N'N'terminal-DRB1 0101 terminal 15-mers B2705- 10-mers Each peptide js a portion of Table XLVIII-109P1 D4v. 6 Table XXII- SEQ lD NO : 13 ; each start N'terminal-DRB1 0401 109P1 D4v. 7 position is specified, the 15-mers N'terminal-A1 length of peptide is 15 amino 9-mers Each peptide is a portion of acids, and the end position for SEQ ID NO : 13 ; each start Each peptide is a each peptide is the start position is specified, the portion of SEQ ID position plus fourteen _j length of peptide is 15 amino NO : 15 ; each start acids, and the end position for position is specified, 19 NCHKCLLSG |E each peptide is the start the length of m _ I position pius fourteen peptide is 9 amino acids, and the end 1911 ISSVVRVNTTNCHKC | E position for each I 10 SSWRVNTTNCHKL 16 peptide is the start | CHKCLLSGTYIFAVL |i | ISSVVRVNTTNCHKC | CHKCLLSGTY. FAVL SSWRVNTTNCHKC 22 KCLLSGTYIFAVLLV 16 10 SSWRVNTTNCHhCCL 14 14 SLSPLLLVS 14 F2211 KCLLSGTYIFAVLLV 16 191 H E F S| NSDISSVVRVNTTNC |E SlSSSSLSPLLlW 1l SSSSLSPLL 8 Table XLIX-109P1 D4v. 6 Table XLVII-1 09P1 D4v. 6 N'terminal-DRB1 1101 Table XXIII- N'terminal-DRB1 0301 15-mers 109P1 D4v. 7 15-mers Each peptide is a portion of N'terminal-A0201 Each peptide is a portion of SEQ ID NO : 13 ; each start 9-mers SEQ ID NO : 13 ; each start position is specified, the Each peptide is a Each peptide is a position is specified, the length of peptide is 15 amino portion of SEQ ID length of peptide is 15 amino acids, and the end position for N0 : 15 ; each start acids, and the end position for each peptide is the start position is specified, each peptide is the start position plus fourteen the length of peptide position plus fourteen is 9 amino acids, 6 NSDISSVVRVNTTNC 22 and the end position 2 TVGFNSD1SSVVRVN 19 for each peptide is X| TVGFNSDISSVVRVN |S W| NSDISSVVRVNTTNC| j 1 E|NSDISSVVRVNTTNC|HI | HKCLLSGTYIFAVLL |g H|RVNTTNCHKCLLSGT|RI I mjTVGFNSDISSVVRVN| E 11 1, F2111 HKCLLSGTYIFAVLL TUTVGFNSDiSSVVRVN F ? Fgll issvv ln2 H 2n4 9 ISSVVRVNTTNCHKC 12 10 SSVVRVNTTNCNKCL 12 Table XXII-15 LSPLLLVSV 21 20 CHKCLLSGTYIFAVL g 109P1D4v. 7 X SSLSPLLLV|E| 12 VVRVNTTNCNKCLLS 11 N'terminal-A1 14 SLSPLLLVS 20 2| KCLLSGTYIFAVLLV 11 9-mers- Each peptide is a 18 TNCHKCLLSGTYiFA 10 Each peptide is a- portion of SEQ ID 10 SSSSSLSPL 16 NO : 15 ; each start 19 LLVSV_VRVN 16 Table XLVIII-109P1D4v. 6 position is specified, N'terminal-DRB1 0401 the length of 15-mers peptide is 9 amino acids, and the end Table XXIV- Each peptide is a porCion of position for each 109P1 D4v. 7 SEQ ID NO : 13 ; each start peptide is the start position is specified, the position plus eight length of peptide is 15 amino A0203 acids, and the end position for 9-mers each peptide is the start 13 SSLSPLLLV 15 position plus fourteen Found. Table XXVII Table XXVIII Table XXV 109P1D4v. 7 109P1D4v. 7 109P1D4v. 7 N'terminal-B0702 N'terminal-B08 N'terminal-A3 9-mers 9-mers 9-mers Each peptide is a Each peptide is a Each peptide is a portion of SEQ ID portion of SEQ ID portion of SEQ ID NO : 15 ; each start NO : 15 ; each start NO : 15 ; each start position is specified, position is specified, position is specified, the length of peptide the length of peptide the length of peptide is 9 amino acids, is 9 amino acids, is 9 amino acids, and the end position and the end position and the end position for each peptide is for each peptide is for each peptide is the start position the start position the start position plus eight plus eight plus eight 16 SPLLLVSW 18 19 LLVSWRVN 17 PLLLVSVVR 26 12 SSSLSPLLL 14 14 SLSPLLLVS 21 10 SSSSSLSPL 13 Table XXIX FFLIISSSSS 109PID4v. 7 3 RVGFLIISS |g | MFRVGFLII | | 9-mers 1 R7 LIISSSSSL 16 13 SSLSPLLLV 11 Each peptide is a S|LL_VSVVRV|E W|LVSVVRVNT|E portion of SEQ ID 20 LVSVVRVNT 16 7 LIISSSSSL 10 N0 : 15 ; each start position is specified, B m I LLLVS the length of peptide F _SSSSLS 1g is 9 amino acids, and the end position Table XXVIII for each peptide is Table XXVI 10SPlD4v. 7 the start position 109P1 D4v. 7 N'terminal-B08. plus eight N'terminal-A26 9-mers 9-mers Each peptide is a Each peptide is a portion of SEQ ID 12 portion of SEQ ID NO : 15 ; each start 12 SSSLSPLLL 12 NO : 15 ; each start position is specified, position is specified, the length of peptide 90 SSSSSLSPL 11 7 LIISSSSSL 10 the length of peptide is 9 amino acids, is 9 amino acids, and the end position F LLLVSVVRV|E and the end position for each peptide is for each peptide is the start position the start position plus eight Table XXX plus eight 109P1D4v. 7 N'terminal-B2705 FL LIISSSSSL 14 9-mers 7 LIISSSSSL 19 1 MFRVGFLII 13 Each peptide is a 3 RVGFLiISS 17 12 SSSLSPLLL 13 portion of SEQ ID lfl 9 Fs-s s-L s P-L L L 10 SSSSSLSPL 15 10 SSSSSLSPL 12 N0 : 15 ; each start m| VGFLIISSS |S H| SSSSLSPLL |S |the length of peptide| |SSSSLSPLL| E|VSVVRVNTT|E I is 9 amino acids, 12 SSSLSPLLL 10 16 SPLLLVSW 10 and the end position for each peptide is 20 LVSVVRVNT 10 18 LLLVSWRV 9 the start position 94 SLSPLLLVS 8 plus eight M| PLLLVSVVR| l FPLLLVSVVRI mI LIISSSSSL 1R . EEFl-6] 1 Table XXX Table XXXU Each peptide is a 109P1D4v. 7 109P1D4v. 7 portion of SEQ ID N'terminal-B2705 N'terminal-B4402 NO : 15 ; each start 9-mers 9-mers position is specified, Each peptide is a Each peptide is a the length of peptide is 10 amino acids, portion of SEQ ID portion of SEQ ID is 10 amino acids, NO : 15 ; each start NO : 15 ; each start and the end position position is specified, position is specified, for each peptide is the length of peptide the length of peptide nine is 9 amino acids, is 9 amino acids, and the end position and the end position for each peptide is for each peptide is the start position I the start position plus eight plus eight I SSSLSPLLLVI 14 PFSSLSPLLLVS ln3 F2] FRVGFLIIS lii g|SSSLSPLLL|i H|SSSSSLSPLL|E 10 SSSSSLSPL 13 7 LIISSSSSL 13 14 SL_SPLLLVSV 11 SSSSLSPLL 13 10 SSSSSLSPL 13 12 SSSLSPLLL 13 11 SSSSLSPLL 13 Table XXXV == =L= == =L= 109P1 D4v. 7 | RVGFLIISS | 2| MFRVGFLII | N'terminal IFVGFLIISS SLSPLLLVS 8 A0201-1 0-mers Each peptide is a portion of SEQ ID 109P1 D4v. 7 N0 : 15 ; each start N'terminal-B5101 position is specified, Table XXXI 9-mers the length of peptide 109P1D4v. 7 is 10 amino acids, N'terminal-B2709 Each peptide is a and the end position 9-mers portion of SEQ ID for each peptide is the NO : 15 ; each start start position plus Each peptide is a position is specified, nine portion of SEQ ID the length of NO : 15 ; each start peptide is 9 amino position is specified, acids, and the end 14 SLSPLLLVSV 32 the length of peptide position for each Rt FLIISSSSSL 25 is 9 amino acids, peptide is the start and the end postition for each peptide is position plus eight 17 PLLLVSVVRV 25 the start position m ll the start position 11 I 11 plus eight 16 SPLLLVSVV 25 19 LL. VSVVRVNT 18 18 LLLVSVVRV 17 12 SSSLSPLLLV 17 l |. 18 LLLVSWRV 13 1 MFRVGFLII 13 20 LVSWRVNTT 17 F El----F131 H 11 SSSSLSPLL 12 15 LSPLLLVSW 16 13 SSLSPLLLV 12 Table XXXIV 109Pl D4v. 7 Table N'terminal-A1 XXXVI 9 ISSSSSLSPL} 10-mers l 109P1D4V@7 12 SSSLSPLLL 11 N'terminal |g|SPLLLVSWß A0203-10- mers MFRVGFLII 9 15 LSPLLLVSV 9 No Results Found. Table XXXVII Table XXXIX No Results 109P1D4v. 7 109P1 D4v. 7 Found. N'terminal-A3 N'terminal-B0702 10-mers 10-mers Table XLIII Eachpeptfdetsa Eachpeptideisa 109P1D4v7 portion of SEQ ID portion of SEQ ID N'terminal- NO : 15 ; each start NO : 15 ; each start B2709 position is specified, position is specified, 10-mers the length of peptide the length of peptide is 10 amino acids, is 10 amino acids, and the end position and the end position No Results for each peptide is the for each peptide is the Found. start position plus start position plus nine nine Table XLIV 09P7 D4v. 7 14 SLSPLLVSV |E W| ISSSSSLSPL} E3 N'terminal-B4402 S RVGFLIISSS 19 11 SSSSLSPLLL 94 10-mers Each peptide is a fez FLIISSSSSL 19 10 SSSSSLSPLL 13 EFPLLL\SVVRV R 17 PLLLVSVVRV 17 16 SPLLLVSWR 13 NO : 15 ; each start F16IFS-PLLLVSWR H position is specified, the length of pbptide is 90 amino acids, 8 IISSSSSLSP 15 12 SSSLSPLLLV 10 and the end position 19 LLVSVVRVNT 15 17 PLLLVSVVRV 9 for each peptide is == = = f== the start position plus 14 9 the start position plus nine 20 LV_SWRVNTT 14 20 LVSVVRVNTT 9 13 SSLSPLLVS 90 15 LSPLLLVSVV 8 11 SSSSLSPLLL 15 HI SSLSPLLLVS lEi SI LSPLLLVSVV 1R HI SSSSLSPLLLlB gil FLIISSSSSL 1D Table XXXVIII Table XL lO9P1D4v. 7 109P1D4v. 7 N'terminal N'terminal- A26-1 O-mers B08 Each peptide is a 10-mers Table XLV portion of SEQ ID 109Pl D4v. 7 NO : 15 ; each start N'terminal- position is specified, Found. 85101 the length of peptide 10-mers is 10 amino acids, and the end position Table XLI for each peptide is the 109P1D4v. 7 No Results start position plus N'terminal-Found. nine B1510 10-mers Table XLVI-109P1 D4v. 7 E RVGFLIISSS 16 0 N'terminal-DRBI 0101 No Results 15-mers 20 LVSVVRVNTT 15 Each peptide is a portion of SEQ ID NO : 15 ; each start 9 ISSSSSLSPL 14 position is specified, the 11 SSSSLSPLLL 11 Table 1LII length of peptide is 15 amino 00 109P1D4v. 7 acids, and the end position for E FRVGFLIISS 10 N'terminal-each peptide is the start B2705 7 LIISSSSSLS 10 10-mers position plus fourteen 10 SSSSSLSPLL 10 El RVGFLIISSS Table XLVI-109P1 D4v. 7 XLVIII-109P1D4v. 7 Table XXII N'terminal-DRB1 0101 N'terminal-DRB1 0401 109PlD4v. 8-A1 15-mers 15-mers 9-mers Each peptide is a portion of Each peptide is a portion of Each peptide is a SEQ ID NO : 15 ; each start SEQ ID NO : 15 ; each start portion of SEQ ID position is specified, the position is specified, the NO : 17 ; each start length of peptide is 15 amino length of peptide is 15 amino position is acids, and the end position for acids, and the end position for specified, the each peptide is the start each peptide is the start length of peptide position plus fourteen position plus fourteen is 9 amino acids, and the end nd th nd posiüon for each 1 MFRVGFLIlSSSSSL 25 3 RVGFLIISSSSSLSP 28 peptide is the s art g| VGFLIISSSSSLSPL 25 77 PLLLVSVVRVNTTNC 26 position plus eighfi H SSSLSPLLLVSWRV T ! MFRVGFLiiSSSSSL [20 HLLSPLLLVSWRVNTT|E S| VGFLIISSSSSLSPL |E @|KKEITVQPT|E T) GFLIISSSSSLSPLL 22 5 GFLIISSSSSLSPLL 20 TFIPGLKKE 8 Wil FLIISSSSSLSPl. LL 22 12 SSSLSPLLLVSWRV 20 9l ISSSSSLSPLLLVSV 22 15 LSPLLLVSWRVNTT 20 Table XXIII 20 LVSVVRVNTTNCHKC 22 18 LLLVSVVRVNTTNCH 20 A020119-me s 2 FRVGFLIISSSSSLS 21 20 LVSWRVNTTNCHKC 20 Each peptide is a 13 SSLSPLLLVSVVRVN |g ELFRVGFLIISSSSSLS |R portion of SEQ ID Ell FLIISSSSSLSPLLL 14 NO : 17 ; each start position is Table XLVII-109PlD4v. 7 16 SPLLLVSVVRVNTTN 14 position is N'terminal-DRB1 0301 specified, the 15-mers VSWRVNTTNCHKCL 14 length of peptide is 15-mers 9 amino acids, and Each peptide is a portion of the end position SEQ ID NO : 15 ; each start Table XLIX-109P1 D4v. 7 for each peptide is position is specified, the N'terminal-DRB1 1101 the start position length of peptide is 15 amino 15-mers plus eight acids, and the end position for Each peptide is a portion of each peptide is the start SEQ ID NO : 15 ; each start position plus fourteen position is specified, the length of peptide is 15 amino I KEITVQPTV 16 4nul VGFLIIS-SS-S-S-LS-P-L] 20 acids, and the end position for lR4 each peptide is the stars 17 PLLLVSVVRVNTTNC 20 position plus fourteen in5 LSPLLLVSVVRVNTT |S I l 5 GFLIISSSSSLSPLL 14 3 RVGFLIISSSSSLSP 22 Table XXIV 109P1 D4v. 8 F6] FLIISSSSSLSPLLL 13 17 PLLLVSVVRVNTTNC 22 A0203-9- 12) SSSLSPLLLVSWRV 13 1 MFRVGFLIISSSSSL 18 mers S| ISSSSSLSPLLLVSV 12 15 LSPLLLVSVVRVNTT 14 0 16 SPLLLVSWRVNTTN 92 l FRVGFLIISSSSSLS 13 No Results 20 LVSVVRVNTTNCNKG 12 GFLIISSSSSLSPLL 13 Found 21 VSVVRVNTTNCHKCL 12 18 LLLVSVVRVNTTNGH 13 3 RVGFLI 91 6 FLIISSSSSLSPLLL 12 10 PlD4v. |S| IISSSSSLSPLLLVS 11 12 SSSLSPLLLVSWRV 12 A3-9-mers 1S1 LLLVSVVRVNTTNCH | W|LVSVVRVNTTNCHKC| S l TH MFRVGFLIISSSSSL 10 16 SPLLLVSWRVNTTN 11 7 LIISSSSSLSPLLLV 1S Each peptide is a Table XXVII Table XXIX portion ofSEQ ID 109P1D4v. 8 109P1D4v. 8 NO : 17 ; each start B0702-9-mers B1510-9-mers position is Each peptide is a Each peptide is a specified, the portion of SEQ ID portion of SEQ ID length of peptide is NO : 17 ; each start NO : 17 ; each 9 amino pepMe s { ; for end position specified, the specified, the foeSSs ' the each peptide is length of peptide length of peptide the start position is 9 amino acids, is 9 amino acids, plus eight and the end and the end position for each position for each 16 peptide is the start peptide is the position plus eight start position plus eight E KElTVQPTvlLl eight l M|KKEITVQPT|E 3 | TFIPGLKKE | N [fli Table XXVIII EFFIPGLKKEIIN 109Pl D4v. 8 El IPGLKKEITIN Table XXVI B08-9-mers Q6 LKKEITVQP 3 Each peptide is a A26-9-mers portion of SEQ ID Each peptide is a NO : 17 ; each start Table XXX portion of SEQ ID position is 109P1D4v. 8 NO : 17 ; each start specified, the B2705-9-mers position is length of peptide is Each peptide is a specified, the 9 amino acids, and portion of SEQ ID length of peptide the end position NO : 17 ; each start is 9 amino acids, for each peptide is position is and the end the start position specified, the position for each plus eight length of peptide is peptide is the start 9 amino acids, and position pius eight I the end position L j l 12 for each peptide is nl 1= grGLKKEITVQ|R the start position 2 FIPGLKKEI 13 plus eight EFFIPGLKKEII KKEiTWE LKKE E F 12] 00 Table XXIX 8 KEITVQPTV 9 m| FIPGLKKEl IE 109P1 D4v. 8 B1510-9-mers B0702-9-mers 4 PGLKKEITV 7 Each peptide is a Each peptide is a portion of SEQ ID portion of SEQ ID NO : 17 ; each Table XXXI NO : 17 ; each start start position is 109P1 D4v. 8 position is specified, the B2709-9-mers specified, the length of peptide length of peptide is 9 amino acids, is 9 amino acids, and the end and the end position for each position for each peptide is the peptide is the start start position plus position plus eight eight I 11 I 3PGLKKEJTJJ18 Each peptide is a Table XXXIV Each peptide is a portion of SEQ ID 109P1 D4v. 8 portion of SEQ ID NO : 17 ; each start A1-10-mers NO : 17 ; each start position is Each peptide is a position is specified, specified, the portion of SEQ ID the length of peptide length of peptide NO : 17 ; each start is 10 amino acids, is 9 amino acids, position is specified, and the end position and the end for ech peptide is pos-tion foreach pepS amino "o ac. sandtheend '--- 'f a posfbon for each peptide is the start acids, and the end plus nine position plus eight acids, and the end position for each 8 KEITVQPTV 12 posit n plus nine GL_KKEITVQP 18 19 HEH- 9FFIPGLKKEiIF8 in 11-0 F (PGLKKEI 8 S_TFIPGLI<I<E 10 KKEITV (PTV 10 Ta6le XXXVIII Table XXXII 109P1 D4v. 8 109P1 D4v. 8 Table XXXV A26-10-mers B4402-9-mers 109P1 D4v. 8 Each peptide is a Each peptide is a A0201-10-mers portion of SEQ ID portion of SEQ ID Each peptide is a NO : 17 ; each start NO : 17 ; each start portion of SEQ ID position is position is NO : 17 ; each start specified, the length specified, the position is specified, of peptide is 10 length of peptide the length of peptide amino acids, and is 9 amino acids, is 10 amino acids, the end position for and the end and the end position each peptide is the position for each for each peptide is start position plus peptide is the start the start position nine position plus eight plus nine l l l l S|STFIPGLKKE|M 8 KEITVQPTV 16 3 FIPGLKKEIT 15 STFIPGLKKE 18 000 00 2 FIPGLKKEI 12 4 IPGLKKEITV 14 Table XXXIX 1 TFIPGLKKE 10 2 TFIPGLKKEI 13 109P1D4v. 8 W|KKEITVQPTV|S B0702-10-mers l Mach peptide is a Table XXXIII 1 STFIPGLKKE 12 portion of SEQ ID B5101-9-mers NO : 17 ; each start position is specified, Each peptide is a LKKEITVQPT] the length of portion of SEQ ID peptide is 10 amino NO : 17 ; each start Table acids, and the end position is XXXVI position for each specified, the 109P1 D4v, 8 peptide is the start length of peptide A0203-1 0-position plus is 9 amino acids, mers and the end position for each 0 W| IPGLKKEITV |S| peptide is the start FFIPGLKKEIT position plus eight Found. 8 Table XXXVII 11 lO9PlD4v. 8 II EFFIPGLKKEIIH A3-1 0-mers Table XL Table XL 3 lPGLKKEIT 13 109P1 D4v. 8 EFKEITVQPTV 9 B08-1 0- mers Table XLVIII-109P1D4v. 8 Table XLV DRB1 0401-15-mers 109Pl D4v. 8 Each peptide is a portion of B51 01-10-SEQ ID NO : 17 ; each start mers position is specified, the Table XLI 109P1 D4v. I. J length of peptide is 15 amino B1510-10-No Results acids, and the end position Found. for each peptide is the start, mer Found. position plus fourteen Table XLVI-I 09PI D4v. 8 DRB10101-15-mers 6 STFIPGLKKEITVQP 20 Found. Each peptide is a portion of iS| IPGLKKEITVQPTVE 20 Table XLII SEQ ID NO : 17 ; each start ESTFIPGLKKEITV7Q 16 109P D4v 8 position Is specffieci, the H|KKEITVQPTVEEASD|E B2705-10-length of peptide is 15 amins mers acids, and the end position | SDPESTFIPGLKKEI 12 for each peptide is the start position plus fourteen No Results 10 PGLKKEITVQPTVEE 12 HIGLKKEITVOPTVFFAG Found. g IPGLKKEITVQPTVE 25 11 GLKKEITVQPTVEEA 12 0 13 KKEITVQPTVEEASD 21 Table XLIII Table XLIX-109PlD4v. 8 109P1 D4v. 8 5 ESTFIPGLKKEITVQ 19 DRB1 1101-15-mers B2709-10-3 DPESTFIPGLKKEIT 17 Each peptide is a portion mers Ell STFIPGLKKE) of SEQ ID NO : 17 ; each start position is specified, No Results the length of peptide is 15 amino acids, and the end Table XLVII-109P1 D4v. 8 position for each peptide is DRB1 0301-15-mers the start position plus Table XLIV fourteen 109P1D4v. 8 Each peptide is a portion of BSl SEQ ! D NO : 17 ; eachstart 11 H|STFIPGLKKEITVQP|E position is specified, the 5 ESTFIPGLKKEITVQ 18 Each peptide is a length of peptide is 15 amino portion of SEQ ID acids, and the end position NO : 17 ; each start for each peptide is the start position is specified, position plus fourteen the length of peptide is 10 amino acids, and the end ESTFIPGLK 17 position for each ! STFIPGLKKEITVQP 17 peptide is the start I| positionplusnine | KKEITVQPTVEEASD| 9 IPGLKKEITVQPTVE 92 |E|KEITVQPTVEX NSDPESTFIPGLKKE|S| 2 TFIPGLKKEI |S| Table L : Protein Characteristics of 109P1D4 109PlD4 var. l Bioinformatic URL on World Wide Web Outcome Program ORF ORF finder 846-3911 bp (includes stop codon) Protein length 1021aa Transmembrane TM Pred. ch. embnet. org/ 3 TM helices (aa3-aa23, aa756- region aa776, aa816-aa834), N terminus intracellular HMMTop. enzim. hu/hmmtop/no TM, N terminus extracellular Sosui. genome. adjp/SOSui/3 TM helices (2-24aa, 756-778aa, 810-832aa), N terminus extra- cellular TMHMM. cbs. dtu. dk/services/TMHMM 1TM helix (813-835aa), N terminus extracellular Signal Peptide Signal P. cbs. dtu. dk/services/SignaIP/ yes pI pI/MW tool. expasy. ch/tools/pI 4. 81 Molecular weight pI/MW tool. expasy. ch/tools/ 112.7kDa Localization PSORT psort. nibb. ac. Plasma membrane PSORT II psort. nibb. ac.jp/ 67% endoplasmic reticulum Motifs Pfam. sanger. ac. uk/Pfam/ Cadherin domain Prints. biochem. ucl. ac. uk/ Cadherin domain, DNA topoiso- Merase 4B, sonic hedgehog Blocks. blocks. fhcrc. org/ Cadherin domain, ribosomal protein L10E, ribulose biphos- phate carboxylase (large chain), ornithine decarboxylase antizyme protein phosphatase 2C subfamily Tab) e U. Exon boundaries of transcript 109P1D4 v. 1 Exon Start End Length 1 1 1385 1385 2 1386 4603 3218 Table LII (a). Nucleotide sequence of transcript variant 109P1 D4 v. 2 (SEQ ID NO : 237) cccctttctc cccctcggtt aagtccctcc ccctcgccat tcaaaagggc tggctcggca 60 ctggctcctt gcagtcggcg aactgtcggg gcgggaggag ccgtgagcag tagctgcact 120 cagctgcccg cgcggcaaag aggaaggcaa gccaaacaga gtgcgcagag tggcagtgcc 180 agcggcgaca caggcagcac aggcagcccg ggctgcctga atagcctcag aaacaacctc 240 agcgactccg gctgctctgc ggactgcgag ctgtggcggt agagcccgct acagcagtcg 300 cagtctccgt ggagcgggcg gaagcctttt ttctcccttt cgtttacctc ttcattctac 360 tctaaaggca tcgttattag gaaaatcctg ttgcgaataa gaaggattcc acagatcaca 420 taccggagag gttttgcctc agctgctctc aactttgtaa tcttgtgaag aagctgacaa 480 gcttggctga ttgcagagca ctatgaggac tgaacgacag tgggttttaa ttcagatatt 540 tcaagtgttg tgcgggttaa tacaacaaac tgtaacaagt gtacctggta tggacttgtt 600 gtccgggacg tacattttcg cggtcctgct agcatgcgtg gtgttccact ctggcgccca 660 ggagaaaaac tacaccatcc gagaagaaat gccagaaaac gtcctgatag gcgacttgtt 720 gaaagacctt aacttgtcgc tgattccaaa caagtccttg acaactgcta tgcagttcaa 780 gctagtgtac aagaccggag atgtgccact gattcgaatt gaagaggata ctggtgagat 840 cttcactact ggcgctcgca ttgatcgtga gaaattatgt gctggtatcc caagggatga 900 gcattgcttt tatgaagtgg aggttgccat tttgccggat gaaatattta gactggttaa 960 gatacgtttt ctgatagaag atataaatga taatgcacca ttgttcccag caacagttat 1020 caacatatca attccagaga actcggctat aaactctaaa tatactctcc cagcggctgt 1080 tgatcctgac gtaggaataa acggagttca aaactacgaa ctaattaaga gtcaaaacat 1140 ttttggcctc gatgtcattg aaacaccaga aggagacaag atgccacaac tgattgttca 1200 aaaggagtta gatagggaag agaaggatac ctacgtgatg aaagtaaagg ttgaagatgg 1260 tggctttcct caaagatcca gtactgctat tttgcaagtg agtgttactg atacaaatga 1320 caaccaccca gtctttaagg agacagagat tgaagtcagt ataccagaaa atgctcctgt 1380 aggcacttca gtgacacagc tccatgccac agatgctgac ataggtgaaa atgccaagat 1440 ccacttctct ttcagcaatc tagtctccaa cattgccagg agattatttc acctcaatgc 1500 caccactgga cttatcacaa tcaaagaacc actggatagg gaagaaacac caaaccacaa 1560 gttactggtt ttggcaagtg atggtggatt gatgccagca agagcaatgg tgctggtaaa 1620 tgttacagat gtcaatgata atgtcccatc cattgacata agatacatcg tcaatcctgt 1680 caatgacaca gttgttcttt cagaaaatat tccactcaac accaaaattg ctctcataac 1740 tgtgacggat aaggatgcgg accataatgg cagggtgaca tgcttcacag atcatgaaat 1800 ccctttcaga ttaaggccag tattcagtaa tcagttcctc ctggagactg cagcatatct 1860 tgactatgag tccacaaaag aatatgccat taaattactg gctgcagatg ctggcaaacc 1920 tcctttgaat cagtcagcaa tgctcttcat caaagtgaaa gatgaaaatg acaatgctcc 1980 agttttcacc cagtctttcg taactgtttc tattcctgag aataactctc ctggcatcca 2040 gttgacgaaa gtaagtgcaa tggatgcaga cagtgggcct aatgctaaga tcaattacct 2100 gctaggccct gatgctccac ctgaattcag cctggattgt cgtacaggca tgctgactgt 2160 agtgaagaaa ctagatagag aaaaagagga taaatattta ttcacaattc tggcaaaaga 2220 taacggggta ccacccttaa ccagcaatgt cacagtcttt gtaagcatta ttgatcagaa 2280 tgacaatagc ccagttttca ctcacaatga atacaacttc tatgtcccag aaaaccttcc 2340 aaggcatggt acagtaggac taatcactgt aactgatcct gattatggag acaattctgc 2400 agttacgctc tccattttag atgagaatga tgacttcacc attgattcac aaactggtgt 2460 catccgacca aatatttcat ttgatagaga aaaacaagaa tcttacactt tctatgtaaa 2520 ggctgaggat ggtggtagag tatcacgttc ttcaagtgcc aaagtaacca taaatgtggt 2580 tgatgtcaat gacaacaaac cagttttcat tgtccctcct tccaactgtt cttatgaatt 2640 ggttctaccg tccactaatc caggcacagt ggtctttcag gtaattgctg ttgacaatga 2700 cactggcatg aatgcagagg ttcgttacag cattgtagga ggaaacacaa gagatctgtt 2760 tgcaatcgac caagaaacag gcaacataac attgatggag aaatgtgatg ttacagacct 2820 tggtttacac agagtgttgg tcaaagctaa tgacttagga cagcctgatt ctctcttcag 2880 tgttgtaatt gtcaatctgt tcgtgaatga gtcggtgacc aatgctacac tgattaatga 2940 actggtgcgc aaaagcactg aagcaccagt gaccccaaat actgagatag ctgatgtatc 3000 ctcaccaact agtgactatg tcaagatcct ggttgcagct gttgctggca ccataactgt 3060 cgttgtagtt attttcatca ctgctgtagt aagatgtcgc caggcaccac accttaaggc 3120 tgctcagaaa aacaagcaga attctgaatg ggctacccca aacccagaaa acaggcagat 3180 gataatgatg aagaaaaaga aaaagaagaa gaagcattcc cctaagaact tgctgcttaa 3240 ttttgtcact attgaagaaa ctaaggcaga tgatgttgac agtgatggaa acagagtcac 3300 actagacctt cctattgatc tagaagagca aacaatggga aagtacaatt gggtaactac 3360 acctactact ttcaagcccg acagccctga tttggcccga cactacaaat ctgcctctcc 3420 acagcctgcc ttccaaattc agcctgaaac tcccctgaat tcgaagcacc acatcatcca 3480 agaactgcct ctcgataaca cctttgtggc ctgtgactct atctccaagt gttcctcaag 3540 cagttcagat ccctacagcg tttctgactg tggctatcca gtgacgacct tcgaggtacc 3600 tgtgtccgta cacaccagac cgactgattc caggacatca actattgaaa tctgcagtga 3660 gatataactt tctaggaaca acaaaattcc attccccttc caaaaaattt caatgattgt 3720 gatttcaaaa ttaggctaag atcattaatt ttgtaatcta gatttcccat tataaaagca 3780 agcaaaaatc atcttaaaaa tgatgtccta gtgaaccttg tgctttcttt agctgtaatc 3840 tggcaatgga aatttaaaat ttatggaaga gacagtgcag cacaataaca gagtactctc 3900 atgctgtttc tctgtttgct ctgaatcaac agccatgatg taatataagg ctgtcttggt 3960 gtatacactt atggttaata tatcagtcat gaaacatgca attacttgcc ctgtctgatt 4020 gttgaataat taaaacatta tctccaggag tttggaagtg agctgaacta gccaaactac 4080 tctctgaaag gtatccaggg caagagacat ttttaagacc ccaaacaaac aaaaaacaaa 4140 accaaaacac tctggttcag tgttttgaaa atattcacta acataatatt gctgagaaaa 4200 tcatttttat tacccaccac tctgcttaaa agttgagtgg gccgggcgcg gtggctcacg 4260 cctgtaatcc cagcactttg ggaggccgag gcgggtggat cacgaggtca ggagattgag 4320 accatcctgg ctaacacggt gaaaccccat ctccactaaa aatacaaaaa attagcctgg 4380 cgtggtggcg ggcgcctgta gtcccagcta ctcgggaggc tgaggcagga gaatagcgtg 4440 aacccgggag gcggagcttg cagtgagccg agatggcgcc actgcactcc agcctgggtg 4500 acagagcaag actctgtctc aaaaagaaaa aaatgttcaa tgatagaaaa taattttact 4560 aggtttttat gttgattgta ctcatgctgt tccactcctt ttaattatta aaaagttatt 4620 tttggctggg tgtggtggct cacacctgta atcccagcac tttgggaggc cgaggtgggt 4680 ggatcacctg aggtcaggag ttcaagacca gtctggccaa cat 4723 Table LIII (a). Nucleotide sequence alignment of 109P1D4 v. 1 (SEQ ID NO : 238) and 109P1D4 v. 2 (SEQ ID NO : 239) Score = 5920 bits (3079), Expect = O. Oldentities = 3079/3079 (100%) Strand = Plus/Plus V. 1 : 800 agtgttgtgcgggttaatacaacaaactgtaacaagtgtacctggtatggacttgttgtc 859 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 2 : 544 agtgttgtgcgggttaatacaacaaactgtaacaagtgtacctggtatggacttgttgtc 603 V. 1 : 860 cgggacgtacattttcgcggtcctgctagcatgcgtggtgttccactctggcgcccagga 919 Illlllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 2 : 604 cgggacgtacattttcgcggtcctgctagcatgcgtggtgttccactctggcgcccagga 663 V. 1 : 920 gaaaaactacaccatccgagaagaaatgccagaaaacgtcctgataggcgacttgttgaa 979 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 2 : 664 gaaaaactacaccatccgagaagaaatgccagaaaacgtcctgataggcgacttgttgaa 723 V. 1 : 980 agaccttaacttgtcgctgattccaaacaagtccttgacaactgctatgcagttcaagct 1039 IIIIllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 2 : 724 agaccttaacttgtcgctgattccaaacaagtccttgacaactgctatgcagttcaagct 783 V. 1 : 1040 agtgtacaagaccggagatgtgccactgattcgaattgaagaggatactggtgagatctt 1099 Illlllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 2 : 784 agtgtacaagaccggagatgtgccactgattcgaattgaagaggatactggtgagatctt 843 V. 1 : 1100 cactactggcgctcgcattgatcgtgagaaattatgtgctggtatcccaagggatgagca 1159 Illllllllllllllllllllllllllllllllllllllllllllllllllllillllll V. 2 : 844 cactactggcgctcgcattgatcgtgagaaattatgtgctggtatcccaagggatgagca 903 V. 1 : 1160 ttgcttttatgaagtggaggttgccattttgccggatgaaatatttagactggttaagat 1219 IIIlllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 2 : 904 ttgcttttatgaagtggaggttgccattttgccggatgaaatatttagactggttaagat 963 V. 1 : 1220 acgttttctgatagaagatataaatgataatgcaccattgttcccagcaacagttatcaa 1279 Illlllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 2 : 964 acgttttctgatagaagatataaatgataatgcaccattgttcccagcaacagttatcaa 1023 V. 1 : 1280 catatcaattccagagaactcggctataaactctaaatatactctcccagcggctgttga 1339 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 2 : 1024 catatcaattccagagaactcggctataaactctaaatatactctcccagcggctgttga 1083 V. 1 : 1340 tcctgacgtaggaataaacggagttcaaaactacgaactaattaagagtcaaaacatttt 1399 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 2 : 1084 tcctgacgtaggaataaacggagttcaaaactacgaactaattaagagtcaaaacatttt 1143 V. 1 : 1400 tggcctcgatgtcattgaaacaccagaaggagacaagatgccacaactgattgttcaaaa 1459 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 2 : 1144 tggcctcgatgtcattgaaacaccagaaggagacaagatgccacaactgattgttcaaaa 1203 V. 1 : 1460 ggagttagatagggaagagaaggatacctacgtgatgaaagtaaaggttgaagatggtgg 1519 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 2 : 1204 ggagttagatagggaagagaaggatacctacgtgatgaaagtaaaggttgaagatggtgg 1263 V. 1 : 1520 ctttcctcaaagatccagtactgctattttgcaagtgagtgttactgatacaaatgacaa 1579 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 2 : 1264 ctttcctcaaagatccagtactgctattttgcaagtgagtgttactgatacaaatgacaa 1323 V. 1 : 1580 ccacccagtctttaaggagacagagattgaagtcagtataccagaaaatgctcctgtagg 1639 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 2 : 1324 ccacccagtctttaaggagacagagattgaagtcagtataccagaaaatgctcctgtagg 1383 V. 1 : 1640 cacttcagtgacacagctccatgccacagatgctgacataggtgaaaatgccaagatcca 1699 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 2 : 1384 cacttcagtgacacagctccatgccacagatgctgacataggtgaaaatgccaagatcca 1443 V. 1 : 1700 cttctctttcagcaatctagtctccaacattgccaggagattatttcacctcaatgccac 1759 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 2 : 1444 cttctctttcagcaatctagtctccaacattgccaggagattatttcacctcaatgccac 1503 V. 1 : 1760 cactggacttatcacaatcaaagaaccactggatagggaagaaacaccaaaccacaagtt 1819 Illlllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 2 : 1504 cactggacttatcacaatcaaagaaccactggatagggaagaaacaccaaaccacaagtt 1563 V. 1 : 1820 actggttttggcaagtgatggtggattgatgccagcaagagcaatggtgctggtaaatgt 1879 Illlllllllllllllllllllllllllllflllllllllllllllllllllllllllll V. 2 : 1564 actggttttggcaagtgatggtggattgatgccagcaagagcaatggtgctggtaaatgt 1623 V. 1 : 1880 tacagatgtcaatgataatgtcccatccattgacataagatacatcgtcaatcctgtcaa 1939 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 2 : 1624 tacagatgtcaatgataatgtcccatccattgacataagatacatcgtcaatcctgtcaa 1683 V. 1 : 1940 tgacacagttgttctttcagaaaatattccactcaacaccaaaattgctctcataactgt 1999 illlllllllllllllllflllllllllllllllllllllllllllllllllllllllll V. 2 : 1684 tgacacagttgttctttcagaaaatattccactcaacaccaaaattgctctcataactgt 1743 V. 1 : 2000 gacggataaggatgcggaccataatggcagggtgacatgcttcacagatcatgaaatccc 2059 Illllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 2 : 1744 gacggataaggatgcggaccataatggcagggtgacatgcttcacagatcatgaaatccc 1803 V. 1 : 2060 tttcagattaaggccagtattcagtaatcagttcctcctggagactgcagcatatcttga 2119 Illllllllillllllflllllllllllllllllllllllllllllllllllllllllll V. 2 : 1804 tttcagattaaggccagtattcagtaatcagttcctcctggagactgcagcatatcttga 1863 V. 1 : 2120 ctatgagtccacaaaagaatatgccattaaattactggctgcagatgctggcaaacctcc 2179 Illlllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 2 : 1864 ctatgagtccacaaaagaatatgccattaaattactggctgcagatgctggcaaacctcc 1923 V. 1 : 2180 tttgaatcagtcagcaatgctcttcatcaaagtgaaagatgaaaatgacaatgctccagt 2239 Illlllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 2 : 1924 tttgaatcagtcagcaatgctcttcatcaaagtgaaagatgaaaatgacaatgctccagt 1983 V. 1 : 2240 tttcacccagtctttcgtaactgtttctattcctgagaataactctcctggcatccagtt 2299 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 2 : 1984 tttcacccagtctttcgtaactgtttctattcctgagaataactctcctggcatccagtt 2043 V. 1 : 2300 gacgaaagtaagtgcaatggatgcagacagtgggcctaatgctaagatcaattacctgct 2359 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 2 : 2044 gacgaaagtaagtgcaatggatgcagacagtgggcctaatgctaagatcaattacctgct 2103 V. 1 : 2360 aggccctgatgctccacctgaattcagcctggattgtcgtacaggcatgctgactgtagt 2419 Illlllllllllllllllllllllllllllllllllllllllllllllllllllllilll V. 2 : 2104 aggccctgatgctccacctgaattcagcctggattgtcgtacaggcatgctgactgtagt 2163 V. 1 : 2420 gaagaaactagatagagaaaaagaggataaatatttattcacaattctggcaaaagataa 2479 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 2 : 2164 gaagaaactagatagagaaaaagaggataaatatttattcacaattctggcaaaagataa 2223 V. 1 : 2480 cggggtaccacccttaaccagcaatgtcacagtctttgtaagcattattgatcagaatga 2539 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 2 : 2224 cggggtaccacccttaaccagcaatgtcacagtctttgtaagcattattgatcagaatga 2283 V. 1 : 2540 caatagcccagttttcactcacaatgaatacaacttctatgtcccagaaaaccttccaag 2599 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 2 : 2284 caatagcccagttttcactcacaatgaatacaacttctatgtcccagaaaaccttccaag 2343 V. 1 : 2600 gcatggtacagtaggactaatcactgtaactgatcctgattatggagacaattctgcagt 2659 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 2 : 2344 gcatggtacagtaggactaatcactgtaactgatcctgattatggagacaattctgcagt 2403 V. 1 : 2660 tacgctctccattttagatgagaatgatgacttcaccattgattcacaaactggtgtcat 2719 IIIIIIIIIllllllllllllllllllllllllllllllllllllllllllllllllll V. 2 : 2404 tacgctctccattttagatgagaatgatgacttcaccattgattcacaaactggtgtcat 2463 V. 1 : 2720 ccgaccaaatatttcatttgatagagaaaaacaagaatcttacactttctatgtaaaggc 2779 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 2 : 2464 ccgaccaaatatttcatttgatagagaaaaacaagaatcttacactttctatgtaaaggc 2523 V. 1 : 2780 tgaggatggtggtagagtatcacgttcttcaagtgccaaagtaaccataaatgtggttga 2839 1111111111|1111111111111111111111111111111111111111111111111 V. 2 : 2524 tgaggatggtggtagagtatcacgttcttcaagtgccaaagtaaccataaatgtggttga 2583 V. 1 : 2840 tgtcaatgacaacaaaccagttttcattgtccctccttccaactgttcttatgaattggt 2899 llllllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 2 : 2584 tgtcaatgacaacaaaccagttttcattgtccctccttccaactgttcttatgaattggt 2643 V. 1 : 2900 tctaccgtccactaatccaggcacagtggtctttcaggtaattgctgttgacaatgacac 2959 llllllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 2 : 2644 tctaccgtccactaatccaggcacagtggtctttcaggtaattgctgttgacaatgacac 2703 V. 1 : 2960 tggcatgaatgcagaggttcgttacagcattgtaggaggaaacacaagagatctgtttgc 3019 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 2 : 2704 tggcatgaatgcagaggttcgttacagcattgtaggaggaaacacaagagatctgtttgc 2763 V. 1 : 3020 aatcgaccaagaaacaggcaacataacattgatggagaaatgtgatgttacagaccttgg 3079 IIIIllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 2 : 2764 aatcgaccaagaaacaggcaacataacattgatggagaaatgtgatgttacagaccttgg 2823 V. 1 : 3080 tttacacagagtgttggtcaaagctaatgacttaggacagcctgattctctcttcagtgt 3139 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 2 : 2824 tttacacagagtgttggtcaaagctaatgacttaggacagcctgattctctcttcagtgt 2883 V. 1 : 3140 tgtaattgtcaatctgttcgtgaatgagtcggtgaccaatgctacactgattaatgaact 3199 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 2 : 2884 tgtaattgtcaatctgttcgtgaatgagtcggtgaccaatgctacactgattaatgaact 2943 V. 1 : 3200 ggtgcgcaaaagcactgaagcaccagtgaccccaaatactgagatagctgatgtatcctc 3259 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 2 : 2944 ggtgcgcaaaagcactgaagcaccagtgaccccaaatactgagatagctgatgtatcctc 3003 V. 1 : 3260 accaactagtgactatgtcaagatcctggttgcagctgttgctggcaccataactgtcgt 3319 Illlllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 2 : 3004 accaactagtgactatgtcaagatcctggttgcagctgttgctggcaccataactgtcgt 3063 V. 1 : 3320 tgtagttattttcatcactgctgtagtaagatgtcgccaggcaccacaccttaaggctgc 3379 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 2 : 3064 tgtagttattttcatcactgctgtagtaagatgtcgccaggcaccacaccttaaggctgc 3123 V. 1 : 3380 tcagaaaaacaagcagaattctgaatgggctaccccaaacccagaaaacaggcagatgat 3439 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 2 : 3124 tcagaaaaacaagcagaattctgaatgggctaccccaaacccagaaaacaggcagatgat 3183 V. 1 : 3440 aatgatgaagaaaaagaaaaagaagaagaagcattcccctaagaacttgctgcttaattt 3499 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 2 : 3184 aatgatgaagaaaaagaaaaagaagaagaagcattcccctaagaacttgctgcttaattt 3243 V. 1 : 3500 tgtcactattgaagaaactaaggcagatgatgttgacagtgatggaaacagagtcacact 3559 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII s V. 2 : 3244 tgtcactattgaagaaactaaggcagatgatgttgacagtgatggaaacagagtcacact 3303 V. 1 : 3560 agaccttcctattgatctagaagagcaaacaatgggaaagtacaattgggtaactacacc 3619 Illllllllllllllllllllllllllllllfllllllllllllllllllllllllllll V. 2 : 3304 agaccttcctattgatctagaagagcaaacaatgggaaagtacaattgggtaactacacc 3363 V. 1 3620 tactactttcaagcccgacagccctgatttggcccgacactacaaatctgcctctccaca 3679 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIlllllllll V. 2 : 3364 tactactttcaagcccgacagccctgatttggcccgacactacaaatctgcctctccaca 3423 V. 1 : 3680 gcctgccttccaaattcagcctgaaactcccctgaattcgaagcaccacatcatccaaga 3739 IIIIIIIIIIilllllllllllllllllllllllllllllllllllllllllllllllll V. 2 : 3424 gcctgccttccaaattcagcctgaaactcccctgaattcgaagcaccacatcatccaaga 3483 V. 1 : 3740 actgcctctcgataacacctttgtggcctgtgactctatctccaagtgttcctcaagcag 3799 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 2 : 3484 actgcctctcgataacacctttgtggcctgtgactctatctccaagtgttcctcaagcag 3543 V. 1 : 3800 ttcagatccctacagcgtttctgactgtggctatccagtgacgaccttcgaggtacctgt 3859 Illlllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 2 : 3544 ttcagatccctacagcgtttctgactgtggctatccagtgacgaccttcgaggtacctgt 3603 V. 1 : 3860 gtccgtacacaccagaccg 3878 11111111111111111l1 V. 2 : 3604 gtccgtacacaccagaccg 3622 Table LIV (a). Peptide sequences of protein coded by 109P1D4 v. 2 (SEQ ID NO : 240) MRTERQWVLI QIFQVLCGLI QQTVTSVPGM DLLSGTYIFA VLLACVVFHS GAQEKNYTIR 60 EEMPENVLIG DLLKDLNLSL IPNKSLTTAM QFKLVYKTGD VPLIRIEEDT GEIFTTGARI 120 DREKLCAGIP RDEHCFYEVE VAILPDEIFR LVKIRFLIED INDNAPLFPA TVINISIPEN 180 SAINSKYTLP AAVDPDVGIN GVQNYELIKS QNIFGLDVIE TPEGDKMPQL IVQKELDREE 240 KDTYVMKVKV EDGGFPQRSS TAILQVSVTD TNDNHPVFKE TEIEVSIPEN APVGTSVTQL 300 HATDADIGEN AKIHFSFSNL VSNIARRLFH LNATTGLITI KEPLDREETP NHKLLVLASD 360 GGLMPARAMV LVNVTDVNDN VPSIDIRYIV NPVNDTVVLS ENIPLNTKIA LITVTDKDAD 420 HNGRVTCFTD HEIPFRLRPV FSNQFLLETA AYLDYESTKE YAIKLLAADA GKPPLNQSAM 480 LFIKVKDEND NAPVFTQSFV TVSIPENNSP GIQLTKVSAM DADSGPNAKI NYLLGPDAPP 540 EFSLDCRTGM LTVVKKLDRE KEDKYLFTIL AKDNGVPPLT SNVTVFVSII DQNDNSPVFT 600 HNEYNFYVPE NLPRHGTVGL ITVTDPDYGD NSAVTLSILD ENDDFTIDSQ TGVIRPNISF 660 DREKQESYTF YVKAEDGGRV SRSSSAKVTI NWDVNDNKP VFIVPPSNCS YELVLPSTNP 720 GTVVFQVIAV DNDTGMNAEV RYSIVGGNTR DLFAIDQETG NITLMEKCDV TDLGLHRVLV 780 KANDLGQPDS LFSWIVNLF VNESVTNATL INELVRKSTE APVTPNTEIA DVSSPTSDYV 840 KILVAAVAGT ITWWIFIT AWRCRQAPH LKAAQKNKQN SEWATPNPEN RQMIMMKKKK 900 KKKKHSPKNL LLNFVTIEET KADDVDSDGN RVTLDLPIDL EEQTMGKYNW VTTPTTFKPD 960 SPDLARHYKS ASPQPAFQIQ PETPLNSKHH IIQELPLDNT FVACDSISKC SSSSSDPYSV 1020 SDCGYPVTTF EVPVSVHTRP TDSRTSTIEI CSEI 1054 Table LV(a). Amino acid sequence alignment of 109P1D4 v.1 (SEQ ID NO : 241) and 109P1D4 v.2 (SEQ ID NO: 242) Score = 2006 bits (5197), Expect = O. Oldentities = 1012/1017 (99%), Positives = 1013/1017 (99%) V. 1 : 1 MDLLSGTYIFAVLLACVVFHSGAQEKNYTIREEMPENVLIGDLLKDLNLSLIPNKSLTTA 60 MDLLSGTYIFAVLLACWFHSGAQEKNYTIREEMPENVLIGDLLKDLNLSLIPNKSLTTA V. 2 : 30 MDLLSGTYIFAVLLACVVFHSGAQEKNYTIREEMPENVLIGDLLKDLNLSLIPNKSLTTA 89 V. 1 : 61 MQFKLVYKTGDVPLIRIEEDTGEIFTTGARIDREKLCAGIPRDEHCFYEVEVAILPDEIF 120 MQFKLVYKTGDVPLIRIEEDTGEIFTTGARIDREKLCAGIPRDEHCFYEVEVAILPDEIF V. 2 : 90 MQFKLVYKTGDVPLIRIEEDTGEIFTTGARIDREKLCAGIPRDEHCFYEVEVAILPDEIF 149 V. 1 : 121 RLVKIRFLIEDINDNAPLFPATVINISIPENSAINSKYTLPAAVDPDVGINGVQNYELIK 180 RLVKIRFLIEDINDNAPLFPATVINISIPENSAINSKYTLPAAVDPDVGINGVQNYELIK V. 2 : 150 RLVKIRFLIEDINDNAPLFPATVINISIPENSAINSKYTLPAAVDPDVGINGVQNYELIK 209 V. 1 : 181 SQNIFGLDVIETPEGDKMPQLIVQKELDREEKDTYVMKVKVEDGGFPQRSSTAILQVSVT 240 SQNIFGLDVIETPEGDKMPQLIVQKELDREEKDTYVMKVKVEDGGFPQRSSTAILQVSVT V. 2 : 210 SQNIFGLDVIETPEGDKMPQLIVQKELDREEKDTYVMKVKVEDGGFPQRSSTAILQVSVT 269 V. 1 241 DTNDNHPVFKETEIEVSIPENAPVGTSVTQLHATDADIGENAKIHFSFSNLVSNIARRLF 300 DTNDNHPVFKETEIEVSIPENAPVGTSVTQLHATDADIGENAKIHFSFSNLVSNIARRLF V. 2 : 270 DTNDNHPVFKETEIEVSIPENAPVGTSVTQLHATDADIGENAKIHFSFSNLVSNIARRLF 329 V. 1 : 301 HLNATTGLITIKEPLDREETPNHKLLVLASDGGLMPARAMVLVNVTDVNDNVPSIDIRYI 360 HLNATTGLITIKEPLDREETPNHKLLVLASDGGLMPARAMVLVNVTDVNDNVPSIDIRYI V. 2 : 330 HLNATTGLITIKEPLDREETPNHKLLVLASDGGLMPARAMVLVNVTDVNDNVPSIDIRYI 389 V. 1 : 361 VNPVNDTVVLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLET 420 VNPVNDTWLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLET V. 2 : 390 VNPVNDTWLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLET 449 V. 1 : 421 AAYLDYESTKEYAIKLLAADAGKPPLNQSAMLFIKVKDENDNAPVFTQSFVTVSIPENNS 480 AAYLDYESTKEYAIKLLAADAGKPPLNQSAMLFIKVKDENDNAPVFTQSFVTVSIPENNS V. 2 : 450 AAYLDYESTKEYAIKLLAADAGKPPLNQSAMLFIKVKDENDNAPVFTQSFVTVSIPENNS 509 V. 1 : 481 PGIQLTKVSAMDADSGPNAKINYLLGPDAPPEFSLDCRTGMLTWKKLDREKEDKYLFTI 540 PGIQLTKVSAMDADSGPNAKINYLLGPDAPPEFSLDCRTGMLTWKKLDREKEDKYLFTI V. 2 : 510 PGIQLTKVSAMDADSGPNAKINYLLGPDAPPEFSLDCRTGMLTWKKLDREKEDKYLFTI 569 V. 1 : 541 LAKDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEYNFYVPENLPRHGTVGLITVTDPDYG 600 LAKDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEYNFYVPENLPRHGTVGLITVTDPDYG V. 2 : 570 LAKDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEYNFYVPENLPRHGTVGLITVTDPDYG 629 V. 1 : 601 DNSAVTLSILDENDDFTIDSQTGVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVT 660 DNSAVTLSILDENDDFTIDSQTGVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVT V. 2 : 630 DNSAVTLSILDENDDFTIDSQTGVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVT 689 V. 1 : 661 INWDVNDNKPVFIVPPSNCSYELVLPSTNPGTVVFQVIAVDNDTGMNAEVRYSIVGGNT 720 INVVDVNDNKPVFIVPPSNCSYELVLPSTNPGTWFQVIAVDNDTGMNAEVRYSIVGGNT V. 2 690 INVVDVNDNKPVFIVPPSNCSYELVLPSTNPGTWFQVIAVDNDTGMNAEVRYSIVGGNT 749 V. 1 : 721 RDLFAIDQETGNITLMEKCDVTDLGLHRVLVKANDLGQPDSLFSWIVNLFVNESVTNAT 780 RDLFAIDQETGNITLMEKCDVTDLGLHRVLVKANDLGQPDSLFSWIVNLFVNESVTNAT V. 2 : 750 RDLFAIDQETGNITLMEKCDVTDLGLHRVLVKANDLGQPDSLFSWIVNLFVNESVTNAT 809 V. 1 : 781 LINELVRKSTEAPVTPNTEIADVSSPTSDYVKILVAAVAGTITWWIFITAWRCRQAP 840 LINELVRKSTEAPVTPNTEIADVSSPTSDYVKILVAAVAGTITWWIFITAWRCRQAP V. 2 : 810 LINELVRKSTEAPVTPNTEIADVSSPTSDYVKILVAAVAGTITWWIFITAWRCRQAP 869 V. 1 : 841 HLKAAQKNKQNSEWATPNPENRQMIMMKKKKKKKKHSPKNLLLNFVTIEETKADDVDSDG 900 HLKAAQKNKQNSEWATPNPENRQMIMMKKKKKKKKHSPKNLLLNFVTIEETKADDVDSDG V. 2 : 870 HLKAAQKNKQNSEWATPNPENRQMIMMKKKKKKKKHSPKNLLLNFVTIEETKADDVDSDG 929 V. 1 : 901 NRVTLDLPIDLEEQTMGKYNWVTTPTTFKPDSPDLARHYKSASPQPAFQIQPETPLNSKH 960 NRVTLDLPIDLEEQTMGKYNWVTTPTTFKPDSPDLARHYKSASPQPAFQIQPETPLNSKH V. 2 : 930 NRVTLDLPIDLEEQTMGKYNWVTTPTTFKPDSPDLARHYKSASPQPAFQIQPETPLNSKH 989 V. 1 : 961 HIIQELPLDNTFVACDSISKCSSSSSDPYSVSDCGYPVTTFEVPVSVHTRPVGIQVS 1017 HIIQELPLDNTFVACDSISKCSSSSSDPYSVSDCGYPVTTFEVPVSVHTRP + S V. 2 : 990 HIIQELPLDNTFVACDSISKCSSSSSDPYSVSDCGYPVTTFEVPVSVHTRPTDSRTS 1046 Table LII (b). Nucleotide sequence of transcript variant 109P1 D4 v, 3 (SEQ ID NO : 243) ctggtggtcc agtacctcca aagatatgga atacactcct gaaatatcct gaaaactttt 60 ttttttcaga atcctttaat aagcagttat gtcaatctga aagttgctta cttgtacttt 120 atattaatag ctattcttgt ttttcttatc caaagaaaaa tcctctaatc cccttttcac 180 atgatagttg ttaccatgtt taggcattag tcacatcaac ccctctcctc tcccaaactt 240 ctcttcttca aatcaaactt tattagtccc tcctttataa tgattccttg cctcgtttta 300 tccagatcaa ttttttttca ctttgatgcc cagagctgaa gaaatggact actgtataaa 360 ttattcattg ccaagagaat aattgcattt taaacccata ttataacaaa gaataatgat 420 tatattttgt gatttgtaac aaataccctt tattttccct taactattga attaaatatt 480 ttaattattt gtattctctt taactatctt ggtatattaa agtattatct tttatatatt 540 tatcaatggt ggacactttt ataggtactc tgtgtcattt ttgatactgt aggtatctta 600 tttcatttat ctttattctt aatgtacgaa ttcataatat ttgattcaga acaaatttat 660 cactaattaa cagagtgtca attatgctaa catctcattt actgatttta atttaaaaca 720 gtttttgtta acatgcatgt ttagggttgg cttcttaata atttcttctt cctcttctct 780 ctctcctctt cttttggtca gtgttgtgcg ggttaataca acaaactgta acaagtgtac 840 ctggtatgga cttgttgtcc gggacgtaca ttttcgcggt cctgctagca tgcgtggtgt 900 tccactctgg cgcccaggag aaaaactaca ccatccgaga agaaatgcca gaaaacgtcc 960 tgataggcga cttgttgaaa gaccttaact tgtcgctgat tccaaacaag tccttgacaa 1020 ctgctatgca gttcaagcta gtgtacaaga ccggagatgt gccactgatt cgaattgaag 1080 aggatactgg tgagatcttc actactggcg ctcgcattga tcgtgagaaa ttatgtgctg 1140 gtatcccaag ggatgagcat tgcttttatg aagtggaggt tgccattttg ccggatgaaa 1200 tatttagact ggttaagata cgttttctga tagaagatat aaatgataat gcaccattgt 1260 tcccagcaac agttatcaac atatcaattc cagagaactc ggctataaac tctaaatata 1320 ctctcccagc ggctgttgat cctgacgtag gaataaacgg agttcaaaac tacgaactaa 1380 ttaagagtca aaacattttt ggcctcgatg tcattgaaac accagaagga gacaagatgc 1440 cacaactgat tgttcaaaag gagttagata gggaagagaa ggatacctac gtgatgaaag 1500 taaaggttga agatggtggc tttcctcaaa gatccagtac tgctattttg caagtgagtg 1560 ttactgatac aaatgacaac cacccagtct ttaaggagac agagattgaa gtcagtatac 1620 cagaaaatgc tcctgtaggc acttcagtga cacagctcca tgccacagat gctgacatag 1680 gtgaaaatgc caagatccac ttctctttca gcaatctagt ctccaacatt gccaggagat 1740 tatttcacct caatgccacc actggactta tcacaatcaa agaaccactg gatagggaag 1800 aaacaccaaa ccacaagtta ctggttttgg caagtgatgg tggattgatg ccagcaagag 1860 caatggtgct ggtaaatgtt acagatgtca atgataatgt cccatccatt gacataagat 1920 acatcgtcaa tcctgtcaat gacacagttg ttctttcaga aaatattcca ctcaacacca 1980 aaattgctct cataactgtg acggataagg atgcggacca taatggcagg gtgacatgct 2040 tcacagatca tgaaatccct ttcagattaa ggccagtatt cagtaatcag ttcctcctgg 2100 agactgcagc atatcttgac tatgagtcca caaaagaata tgccattaaa ttactggctg 2160 cagatgctgg caaacctcct ttgaatcagt cagcaatgct cttcatcaaa gtgaaagatg 2220 aaaatgacaa tgctccagtt ttcacccagt ctttcgtaac tgtttctatt cctgagaata 2280 actctcctgg catccagttg acgaaagtaa gtgcaatgga tgcagacagt gggcctaatg 2340 ctaagatcaa ttacctgcta ggccctgatg ctccacctga attcagcctg gattgtcgta 2400 caggcatgct gactgtagtg aagaaactag atagagaaaa agaggataaa tatttattca 2460 caattctggc aaaagataac ggggtaccac ccttaaccag caatgtcaca gtctttgtaa 2520 gcattattga tcagaatgac aatagcccag ttttcactca caatgaatac aacttctatg 2580 tcccagaaaa ccttccaagg catggtacag taggactaat cactgtaact gatcctgatt 2640 atggagacaa ttctgcagtt acgctctcca ttttagatga gaatgatgac ttcaccattg 2700 attcacaaac tggtgtcatc cgaccaaata tttcatttga tagagaaaaa caagaatctt 2760 acactttcta tgtaaaggct gaggatggtg gtagagtatc acgttcttca agtgccaaag 2820 taaccataaa tgtggttgat gtcaatgaca acaaaccagt tttcattgtc cctccttcca 2880 actgttctta tgaattggtt ctaccgtcca ctaatccagg cacagtggtc tttcaggtaa 2940 ttgctgttga caatgacact ggcatgaatg cagaggttcg ttacagcatt gtaggaggaa 3000 acacaagaga tctgtttgca atcgaccaag aaacaggcaa cataacattg atggagaaat 3060 gtgatgttac agaccttggt ttacacagag tgttggtcaa agctaatgac ttaggacagc 3120 ctgattctct cttcagtgtt gtaattgtca atctgttcgt gaatgagtcg gtgaccaatg 3180 ctacactgat taatgaactg gtgcgcaaaa gcactgaagc accagtgacc ccaaatactg 3240 agatagctga tgtatcctca ccaactagtg actatgtcaa gatcctggtt gcagctgttg 3300 ctggcaccat aactgtcgtt gtagttattt tcatcactgc tgtagtaaga tgtcgccagg 3360 caccacacct taaggctgct cagaaaaaca agcagaattc tgaatgggct accccaaacc 3420 cagaaaacag gcagatgata atgatgaaga aaaagaaaaa gaagaagaag cattccccta 3480 agaacttgct gcttaatttt gtcactattg aagaaactaa ggcagatgat gttgacagtg 3540 atggaaacag agtcacacta gaccttccta ttgatctaga agagcaaaca atgggaaagt 3600 acaattgggt aactacacct actactttca agcccgacag ccctgatttg gcccgacact 3660 acaaatctgc ctctccacag cctgccttcc aaattcagcc tgaaactccc ctgaattcga 3720 agcaccacat catccaagaa ctgcctctcg ataacacctt tgtggcctgt gactctatct 3780 ccaagtgttc ctcaagcagt tcagatccct acagcgtttc tgactgtggc tatccagtga 3840 cgaccttcga ggtacctgtg tccgtacaca ccagaccgcc aatgaaggag gttgtgcgat 3900 cttgcacccc catgaaagag tctacaacta tggagatctg gattcatccc caaccacagc 3960 ggaaatctga agggaaagtg gcaggaaagt cccagcggcg tgtcacattt cacctgccag 4020 aaggctctca ggaaagcagc agtgatggtg gactgggaga ccatgatgca ggcagcctta 4080 ccagcacatc tcatggcctg ccccttggct atcctcagga ggagtacttt gatcgtgcta 4140 cacccagcaa tcgcactgaa ggggatggca actccgatcc tgaatctact ttcatacctg 4200 gactaaagaa agctgcagaa ataactgttc aaccaactgt ggaagaggcc tctgacaact 4260 gcactcaaga atgtctcatc tatggccatt ctgatgcctg ctggatgccg gcatctctgg 4320 atcattccag ctcttcgcaa gcacaggcct ctgctctatg ccacagccca ccactgtcac 4380 aggcctctac tcagcaccac agcccacgag tgacacagac cattgctctc tgccacagcc 4440 ctccagtgac acagaccatc gcattgtgcc acagcccacc accgatacag gtgtctgctc 4500 tccaccacag tcctcctcta gtgcaggcta ctgcacttca ccacagccca ccatcagcac 4560 aggcctcagc cctctgctac agccctcctt tagcacaggc tgctgcaatc agccacagct 4620 ctcctctgcc acaggttatt gccctccatc gtagtcaggc ccaatcatca gtcagtttgc 4680 agcaaggttg ggtgcaaggt gctgatgggc tatgctctgt tgatcaggga gtgcaaggta 4740 gtgcaacatc tcagttttac accatgtctg aaagacttca tcccagtgat gattcaatta 4800 aagtcattcc tttgacaacc ttcactccac gccaacaggc cagaccgtcc agaggtgatt 4860 cccccattat ggaagaacat cccttgtaaa gctaaaatag ttacttcaaa ttttcagaaa 4920 agatgtatat agtcaaaatt taagatacaa ttccaatgag tattctgatt atcagatttg 4980 taaataacta tgtaaataga aacagatacc agaataaatc tacagctaga cccttagtca 5040 atagttaacc aaaaaattgc aatttgttta attcagaatg tgtatttaaa aagaaaagga 5100 atttaacaat ttgcatcccc ttgtacagta aggcttatca tgacagagcg cactatttct 5160 gatgtacagt attttttgtt gtttttatca tcatgtgcaa tattactgat ttgtttccat 5220 gctgattgtg tggaaccagt atgtagcaaa tggaaagcct agaaatatct tattttctaa 5280 gtttaccttt agtttaccta aacttttgtt cagataacgt taaaaggtat acgtactcta 5340 gccttttttt gggctttctt tttgattttt gtttgttgtt ttcagttttt ttgttgttgt 5400 tagtgagtct cccttcaaaa tacgcagtag gtagtgtaaa tactgcttgt ttgtgtctct 5460 ctgctgtcat gttttctacc ttattccaat actatattgt tgataaaatt tgtatataca 5520 ttttcaataa agaatatgta taaactgtac agatctagat ctacaaccta tttctctact 5580 ctttagtaga gttcgagaca cagaagtgca ataactgccc taattaagca actatttgtt 5640 aaaaagggcc tctttttact ttaatagttt agtgtaaagt acatcagaaa taaagctgta 5700 tctgccattt taagcctgta gtccattatt acttgggtct ttacttctgg gaatttgtat 5760 gtaacagcct agaaaattaa aaggaggtgg atgcatccaa agcacgagtc acttaaaata 5820 tcgacggtaa actactattt tgtagagaaa ctcaggaaga tttaaatgtt gatttgacag 5880 ctcaataggc tgttaccaaa gggtgttcag taaaaataac aaatacatgt aactgtagat 5940 aaaaccatat actaaatcta taagactaag ggatttttgt tattctagct caacttactg 6000 aagaaaacca ctaataacaa caagaatatc aggaaggaac ttttcaagaa atgtaattat 6060 aaatctacat caaacagaat tttaaggaaa aatgcagagg gagaaataag gcacatgact 6120 gcttcttgca gtcaacaaga aataccaata acacacacag aacaaaaacc atcaaaatct 6180 catatatgaa ataaaatata ttcttctaag caaagaaaca gtactattca tagaaaacat 6240 tagttttctt ctgttgtctg ttatttcctt cttgtatcct cttaactggc cattatcttg 6300 tatgtgcaca ttttataaat gtacagaaac atcaccaact taattttctt ccatagcaaa 6360 actgagaaaa taccttgttt cagtataaca ctaaaccaag agacaattga tgtttaatgg 6420 gggcggttgg ggtggggggg ggagtcaata tctcctattg attaacttag acatagattt 6480 tgtaatgtat aacttgatat ttaatttatg attaaactgt gtgtaaattt tgtaacataa 6540 actgtggtaa ttgcataatt tcattggtga ggatttccac tgaatattga gaaagtttct 6600 tttcatgtgc ccagcaggtt aagtagcgtt ttcagaatat acattattcc catccattgt 6660 aaagttcctt aagtcatatt tgactgggcg tgcagaataa cttcttaact tttaactatc 6720 agagtttgat taataaaatt aattaatgtt ttttctcctt cgtgttgtta atgttccaag 6780 ggatttggag catactggtt ttccaggtgc atgtgaatcc cgaaggactg atgatatttg 6840 aatgtttatt aaattattat catacaaatg tgttgatatt gtggctattg ttgatgttga 6900 aaattttaaa cttggggaag attaagaaaa gaaccaatag tgacaaaaat cagtgcttcc 6960 agtagatttt agaacattct ttgcctcaaa aaacctgcaa agatgatgtg agattttttc 7020 ttgtgtttta attattttca cattttctct ctgcaaaact ttagttttct gatgatctac 7080 acacacacac acacacacac gtgcacacac acacacattt aaatgatata aaaagaagag 7140 gttgaaagat tattaaataa cttatcaggc atctcaatgg ttactatcta tgttagtgaa 7200 aatcaaatag gactcaaagt tggatatttg ggatttttct tctgacagta taatttattg 7260 agttactagg gaggttctta aatcctcata tctggaaact tgtgacgttt tgacaccttt 7320 cctatagatg atataggaat gaaccaatac gcttttatta ccctttctaa ctctgatttt 7380 ataatcagac ttagattgtg tttagaatat taaatgactg ggcaccctct tcttggtttt 7440 taccagagag gctttgaatg gaagcaggct gagagtagcc aaagaggcaa ggggtattag 7500 cccagttatt ctcccctatg ccttccttct ctttctaagc gtccactagg tctggccttg 7560 gaaacctgtt acttctaggg cttcagatct gatgatatct ttttcatcac attacaagtt 7620 atttctctga ctgaatagac agtggtatag gttgacacag cacacaagtg gctattgtga 7680 tgtatgatgt atgtagtcct acaactgcaa aacgtcttac tgaaccaaca atcaaaaaat 7740 ggttctgttt taaaaaggat tttgtttgat ttgaaattaa aacttcaagc tgaatgactt 7800 atatgagaat aatacgttca atcaaagtag ttattctatt ttgtgtccat attccattag 7860 attgtgatta ttaattttct agctatggta ttactatatc acacttgtga gtatgtattc 7920 aaatactaag tatcttatat gctacgtgca tacacattct tttcttaaac tttacctgtg 7980 ttttaactaa tattgtgtca gtgtattaaa aattagcttt tacatatgat atctacaatg 8040 taataaattt agagagtaat tttgtgtatt cttatttact taacatttta cttttaatta 8100 tgtaaatttg gttagaaaat aataataaat ggttagtgct attgtgtaat ggtagcagtt 8160 acaaagagcc tctgccttcc caaactaata tttatcacac atggtcatta aatgggaaaa 8220 aaatagacta aacaaatcac aaattgttca gttcttaaaa tgtaattatg tcacacacac 8280 aaaaaatcct tttcaatcct gagaaaatta aaggcgtttt actcacatgg ctatttcaac 8340 attagttttt tttgtttgtt tctttttcat ggtattactg aaggtgtgta tactccctaa 8400 tacacattta tgaaaatcta cttgtttagg cttttattta tactcttctg atttatattt 8460 tttattataa ttattatttc ttatctttct tcttttatat tttttggaaa ccaaatttat 8520 agttagttta ggtaaacttt ttattatgac cattagaaac tattttgaat gcttccaact 8580 ggctcaattg gccgggaaaa catgggagca agagaagctg aaatatattt ctgcaagaac 8640 ctttctatat tatgtgccaa ttaccacacc agatcaattt tatgcagagg ccttaaaata 8700 ttctttcaca gtagctttct tacactaacc gtcatgtgct tttagtaaat atgattttta 8760 aaagcagttc aagttgacaa cagcagaaac agtaacaaaa aaatctgctc agaaaaatgt 8820 atgtgcacaa ataaaaaaaa ttaatggcaa ttgtttagtg attgtaagtg atacttttta 8880 aagagtaaac tgtgtgaaat ttatactatc cctgcttaaa atattaagat ttttatgaaa 8940 tatgtattta tgtttgtatt gtgggaagat tcctcctctg tgatatcata cagcatctga 9000 aagtgaacag tatcccaaag cagttccaac catgctttgg aagtaagaag gttgactatt 9060 gtatggccaa ggatggcagt atgtaatcca gaagcaaact tgtattaatt gttctatttc 9120 aggttctgta ttgcatgttt tcttattaat atatattaat aaaagttatg agaaat 9176 Table bill (b). Nucleotide sequence alignment of 109P1D4 v. 1 (SEQ ID NO : 244) and 109P1D4 v. 3 (SEq ID NO : 245) Score = 7456 bits (3878), Expect = O. Oldentities = 3878/3878 (100%) Strand = Plus/Plus V. 1 : 1 ctggtggtccagtacctccaaagatatggaatacactcctgaaatatcctgaaaactttt 60 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 3 : 1 ctggtggtccagtacctccaaagatatggaatacactcctgaaatatcctgaaaactttt 60 V. 1 : 61 ttttttcagaatcctttaataagcagttatgtcaatctgaaagttgcttacttgtacttt 120 llllllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 3 : 61 ttttttcagaatcctttaataagcagttatgtcaatctgaaagttgcttacttgtacttt 120 V. 1 : 121 atattaatagctattcttgtttttcttatccaaagaaaaatcctctaatccccttttcac 180 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 3 : 121 atattaatagctattcttgtttttcttatccaaagaaaaatcctctaatccccttttcac 180 V. 1 : 181 atgatagttgttaccatgtttaggcattagtcacatcaacccctctcctctcccaaactt 240 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 3 : 181 atgatagttgttaccatgtttaggcattagtcacatcaacccctctcctctcccaaactt 240 V. 1 : 241 ctcttcttcaaatcaaactttattagtccctcctttataatgattccttgcctcgtttta 300 illlllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 3 : 241 ctcttcttcaaatcaaactttattagtccctcctttataatgattccttgcctcgtttta 300 V. 1 : 301 tccagatcaattttttttcactttgatgcccagagctgaagaaatggactactgtataaa 360 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 3 : 301 tccagatcaattttttttcactttgatgcccagagctgaagaaatggactactgtataaa 360 V. 1 : 361 ttattcattgccaagagaataattgcattttaaacccatattataacaaagaataatgat 420 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 3 : 361 ttattcattgccaagagaataattgcattttaaacccatattataacaaagaataatgat 420 V. 1 : 421 tatattttgtgatttgtaacaaataccctttattttcccttaactattgaattaaatatt 480 Illlllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 3 : 421 tatattttgtgatttgtaacaaataccctttattttcccttaactattgaattaaatatt 480 V. 1 : 481 ttaattatttgtattctctttaactatcttggtatattaaagtattatcttttatatatt 540 Illlllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 3 : 481 ttaattatttgtattctctttaactatcttggtatattaaagtattatcttttatatatt 540 V. 1 : 541 tatcaatggtggacacttttataggtactctgtgtcatttttgatactgtaggtatctta 600 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 3 : 541 tatcaatggtggacacttttataggtactctgtgtcatttttgatactgtaggtatctta 600 V. 1 : 601 tttcatttatctttattcttaatgtacgaattcataatatttgattcagaacaaatttat 660 lllllllllllllillllllllllllllllllllllllllllllllllllllllllllll V. 3 : 601 tttcatttatctttattcttaatgtacgaattcataatatttgattcagaacaaatttat 660 V. 1 : 661 cactaattaacagagtgtcaattatgctaacatctcatttactgattttaatttaaaaca 720 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 3 : 661 cactaattaacagagtgtcaattatgctaacatctcatttactgattttaatttaaaaca 720 V. 1 : 721 gtttttgttaacatgcatgtttagggttggcttcttaataatttcttcttcctcttctct 780 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 3 : 721 gtttttgttaacatgcatgtttagggttggcttcttaataatttcttcttcctcttctct 780 V. 1 : 781 ctctcctcttcttttggtcagtgttgtgcgggttaatacaacaaactgtaacaagtgtac 840 IIIllllllllllllllllllllllllllllllllllllllillllllllllllllllll V. 3 781 ctctcctcttcttttggtcagtgttgtgcgggttaatacaacaaactgtaacaagtgtac 840 V. 1 : 841 ctggtatggacttgttgtccgggacgtacattttcgcggtcctgctagcatgcgtggtgt 900 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 3 : 841 ctggtatggacttgttgtccgggacgtacattttcgcggtcctgctagcatgcgtggtgt 900 V. 1 : 901 tccactctggcgcccaggagaaaaactacaccatccgagaagaaatgccagaaaacgtcc 960 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 3 901 tccactctggcgcccaggagaaaaactacaccatccgagaagaaatgccagaaaacgtcc 960 V. 1 : 961 tgataggcgacttgttgaaagaccttaacttgtcgctgattccaaacaagtccttgacaa 1020 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 3 : 961 tgataggcgacttgttgaaagaccttaacttgtcgctgattccaaacaagtccttgacaa 1020 V. 1 : 1021 ctgctatgcagttcaagctagtgtacaagaccggagatgtgccactgattcgaattgaag 1080 IIIIIIIII'Illllllllllllllllllllllllllllllllllllllllll llllllll V. 3. 1021 ctgctatgcagttcaagctagtgtacaagaccggagatgtgccactgattcgaattgaag 1080 V. 1 : 1081 aggatactggtgagatcttcactactggcgctcgcattgatcgtgagaaattatgtgctg 1140 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 3 : 1081 aggatactggtgagatcttcactactggcgctcgcattgatcgtgagaaattatgtgctg 1140 V. 1 : 1141 gtatcccaagggatgagcattgcttttatgaagtggaggttgccattttgccggatgaaa 1200 1111l1111111111111111111111111111111111111111111111111111111 V. 3 : 1141 gtatcccaagggatgagcattgcttttatgaagtggaggttgccattttgccggatgaaa 1200 V. 1 : 1201 tatttagactggttaagatacgttttctgatagaagatataaatgataatgcaccattgt 1260 Illlllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 3 : 1201 tatttagactggttaagatacgttttctgatagaagatataaatgataatgcaccattgt 1260 V. 1 : 1261 tcccagcaacagttatcaacatatcaattccagagaactcggctataaactctaaatata 1320 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 3 : 1261 tcccagcaacagttatcaacatatcaattccagagaactcggctataaactctaaatata 1320 V. 1 : 1321 ctctcccagcggctgttgatcctgacgtaggaataaacggagttcaaaactacgaactaa 1380 111111111111111111111111111111111111111111111|11111111111111 V. 3 : 1321 ctctcccagcggctgttgatcctgacgtaggaataaacggagttcaaaactacgaactaa 1380 V. 1 : 1381 ttaagagtcaaaacatttttggcctcgatgtcattgaaacaccagaaggagacaagatgc 1440 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 3 : 1381 ttaagagtcaaaacatttttggcctcgatgtcattgaaacaccagaaggagacaagatgc 1440 V. 1 : 1441 cacaactgattgttcaaaaggagttagatagggaagagaaggatacctacgtgatgaaag 1500 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 3 : 1441 cacaactgattgttcaaaaggagttagatagggaagagaaggatacctacgtgatgaaag 1500 V. 1 : 1501 taaaggttgaagatggtggctttcctcaaagatccagtactgctattttgcaagtgagtg 1560 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 3 : 1501 taaaggttgaagatggtggctttcctcaaagatccagtactgctattttgcaagtgagtg 1560 V. 1 : 1561 ttactgatacaaatgacaaccacccagtctttaaggagacagagattgaagtcagtatac 1620 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 3 : 1561 ttactgatacaaatgacaaccacccagtctttaaggagacagagattgaagtcagtatac 1620 V. 1 : 1621 cagaaaatgctcctgtaggcacttcagtgacacagctccatgccacagatgctgacatag 1680 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 3 : 1621 cagaaaatgctcctgtaggcacttcagtgacacagctccatgccacagatgctgacatag 1680 V. 1 : 1681 gtgaaaatgccaagatccacttctctttcagcaatctagtctccaacattgccaggagat 1740 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 3 : 1681 gtgaaaatgccaagatccacttctctttcagcaatctagtctccaacattgccaggagat 1740 V. 1 : 1741 tatttcacctcaatgccaccactggacttatcacaatcaaagaaccactggatagggaag 1800 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 3 : 1741 tatttcacctcaatgccaccactggacttatcacaatcaaagaaccactggatagggaag 1800 V. 1 : 1801 aaacaccaaaccacaagttactggttttggcaagtgatggtggattgatgccagcaagag 1860 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 3 : 1801 aaacaccaaaccacaagttactggttttggcaagtgatggtggattgatgccagcaagag 1860 V. 1 : 1861 caatggtgctggtaaatgttacagatgtcaatgataatgtcccatccattgacataagat 1920 IIIIIIIIIIIIIIIIIIIIIIII111111111111111111111111111111111111 V. 3 : 1861 caatggtgctggtaaatgttacagatgtcaatgataatgtcccatccattgacataagat 1920 V. 1 : 1921 acatcgtcaatcctgtcaatgacacagttgttctttcagaaaatattccactcaacacca 1980 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 3 : 1921 acatcgtcaatcctgtcaatgacacagttgttctttcagaaaatattccactcaacacca 1980 V. 1 :1991 aaattgctctcataactgtgacggataaggatgcggaccataatggcagggtgacatgct 2040 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 3 : 1981 aaattgctctcataactgtgacggataaggatgcggaccataatggcagggtgacatgct 2040 V. 1 : 2041 tcacagatcatgaaatccctttcagattaaggccagtattcagtaatcagttcctcctgg 2100 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 3 : 2041 tcacagatcatgaaatccctttcagattaaggccagtattcagtaatcagttcctcctgg 2100 V. 1 : 2101 agactgcagcatatcttgactatgagtccacaaaagaatatgccattaaattactggctg 2160 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIillllllllllllllllllll V. 3 : 2101 agactgcagcatatcttgactatgagtccacaaaagaatatgccattaaattactggctg 2160 V. 1 : 2161 cagatgctggcaaacctcctttgaatcagtcagcaatgctcttcatcaaagtgaaagatg 2220 Illlllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 3 : 2161 cagatgctggcaaacctcctttgaatcagtcagcaatgctcttcatcaaagtgaaagatg 2220 V. 1 : 2221 aaaatgacaatgctccagttttcacccagtctttcgtaactgtttctattcctgagaata 2280 111111111111111111111111111111111111111111111111111111111111 V. 3 : 2221 aaaatgacaatgctccagttttcacccagtctttcgtaactgtttctattcctgagaata 2280 V. 1 : 2281 actctcctggcatccagttgacgaaagtaagtgcaatggatgcagacagtgggcctaatg 2340 IIIlllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 3 : 2281 actctcctggcatccagttgacgaaagtaagtgcaatggatgcagacagtgggcctaatg 2340 V. 1 : 2341 ctaagatcaattacctgctaggccctgatgctccacctgaattcagcctggattgtcgta 2400 Illlllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 3 : 2341 ctaagatcaattacctgctaggccctgatgctccacctgaattcagcctggattgtcgta 2400 V. 1 : 2401 caggcatgctgactgtagtgaagaaactagatagagaaaaagaggataaatatttattca 2460 Illlllllllllllllllllllllllllllllllllllllllllfillllllllllllll V. 3 : 2401 caggcatgctgactgtagtgaagaaactagatagagaaaaagaggataaatatttattca 2460 V. 1 : 2461 caattctggcaaaagataacggggtaccacccttaaccagcaatgtcacagtctttgtaa 2520 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 3 : 2461 caattctggcaaaagataacggggtaccacccttaaccagcaatgtcacagtctttgtaa 2520 V. 1 : 2521 gcattattgatcagaatgacaatagcccagttttcactcacaatgaatacaacttctatg 2580 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 3 : 2521 gcattattgatcagaatgacaatagcccagttttcactcacaatgaatacaacttctatg 2580 V. 1 : 2581 tcccagaaaaccttccaaggcatggtacagtaggactaatcactgtaactgatcctgatt 2640 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 3 : 2581 tcccagaaaaccttccaaggcatggtacagtaggactaatcactgtaactgatcctgatt 2640 V. 1 : 2641 atggagacaattctgcagttacgctctccattttagatgagaatgatgacttcaccattg 2700 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 3 : 2641 atggagacaattctgcagttacgctctccattttagatgagaatgatgacttcaccattg 2700 V. 1 : 2701 attcacaaactggtgtcatccgaccaaatatttcatttgatagagaaaaacaagaatctt 2760 III111111111111111111111111111111111111111111111111111111111 V. 3 : 2701 attcacaaactggtgtcatccgaccaaatatttcatttgatagagaaaaacaagaatctt 2760 V. 1 : 2761 acactttctatgtaaaggctgaggatggtggtagagtatcacgttcttcaagtgccaaag 2820 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 3 : 2761 acactttctatgtaaaggctgaggatggtggtagagtatcacgttcttcaagtgccaaag 2820 V. 1 : 2821 taaccataaatgtggttgatgtcaatgacaacaaaccagttttcattgtccctccttcca 2880 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 3 : 2821 taaccataaatgtggttgatgtcaatgacaacaaaccagttttcattgtccctccttcca 2880 V. 1 : 2881 actgttcttatgaattggttctaccgtccactaatccaggcacagtggtctttcaggtaa 2940 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 3 : 2881 actgttcttatgaattggttctaccgtccactaatccaggcacagtggtctttcaggtaa 2940 V. 1 : 2941 ttgctgttgacaatgacactggcatgaatgcagaggttcgttacagcattgtaggaggaa 3000 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 3 : 2941 ttgctgttgacaatgacactggcatgaatgcagaggttcgttacagcattgtaggaggaa 3000 V. 1 : 3001 acacaagagatctgtttgcaatcgaccaagaaacaggcaacataacattgatggagaaat 3060 11111111111111111111111111111111|111111111111111111111111111 V. 3 : 3001 acacaagagatctgtttgcaatcgaccaagaaacaggcaacataacattgatggagaaat 3060 V. 1 : 3061 gtgatgttacagaccttggtttacacagagtgttggtcaaagctaatgacttaggacagc 3120 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 3 : 3061 gtgatgttacagaccttggtttacacagagtgttggtcaaagctaatgacttaggacagc 3120 V. 1 : 3121 ctgattctctcttcagtgttgtaattgtcaatctgttcgtgaatgagtcggtgaccaatg 3180 flllllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 3 : 3121 ctgattctctcttcagtgttgtaattgtcaatctgttcgtgaatgagtcggtgaccaatg 3180 V. 1 : 3181 ctacactgattaatgaactggtgcgcaaaagcactgaagcaccagtgaccccaaatactg 3240 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 3 : 3181 ctacactgattaatgaactggtgcgcaaaagcactgaagcaccagtgaccccaaatactg 3240 V. 1 : 3241 agatagctgatgtatcctcaccaactagtgactatgtcaagatcctggttgcagctgttg 3300 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 3 : 3241 agatagctgatgtatcctcaccaactagtgactatgtcaagatcctggttgcagctgttg 3300 V. 1 : 3301 ctggcaccataactgtcgttgtagttattttcatcactgctgtagtaagatgtcgccagg 3360 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 3 : 3301 ctggcaccataactgtcgttgtagttattttcatcactgctgtagtaagatgtcgccagg 3360 V. 1 : 3361 caccacaccttaaggctgctcagaaaaacaagcagaattctgaatgggctaccccaaacc 3420 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 3 : 3361 caccacaccttaaggctgctcagaaaaacaagcagaattctgaatgggctaccccaaacc 3420 V. 1 : 3421 cagaaaacaggcagatgataatgatgaagaaaaagaaaaagaagaagaagcattccccta 3480 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 3 : 3421 cagaaaacaggcagatgataatgatgaagaaaaagaaaaagaagaagaagcattccccta 3480 V. 1 : 3481 agaacttgctgcttaattttgtcactattgaagaaactaaggcagatgatgttgacagtg 3540 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 3 : 3481 agaacttgctgcttaattttgtcactattgaagaaactaaggcagatgatgttgacagtg 3540 V. 1 : 3541 atggaaacagagtcacactagaccttcctattgatctagaagagcaaacaatgggaaagt 3600 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 3 : 3541 atggaaacagagtcacactagaccttcctattgatctagaagagcaaacaatgggaaagt 3600 V. 1 : 3601 acaattgggtaactacacctactactttcaagcccgacagccctgatttggcccgacact 3660 IIIlllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 3 : 3601 acaattgggtaactacacctactactttcaagcccgacagccctgatttggcccgacact 3660 V. 1 : 3661 acaaatctgcctctccacagcctgccttccaaattcagcctgaaactcccctgaattcga 3720 IIIlllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 3 : 3661 acaaatctgcctctccacagcctgccttccaaattcagcctgaaactcccctgaattcga 3720 V. 1 : 3721 agcaccacatcatccaagaactgcctctcgataacacctttgtggcctgtgactctatct 3780 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 3 : 3721 agcaccacatcatccaagaactgcctctcgataacacctttgtggcctgtgactctatct 3780 V. 1 : 3781 ccaagtgttcctcaagcagttcagatccctacagcgtttctgactgtggctatccagtga 3840 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 3 : 3781 ccaagtgttcctcaagcagttcagatccctacagcgtttctgactgtggctatccagtga 3840 V. 1 : 3841 cgaccttcgaggtacctgtgtccgtacacaccagaccg 3878 111z1111111111111111111111111111111111 V. 3 : 3841 cgaccttcgaggtacctgtgtccgtacacaccagaccg 3878 Table LIV (b). Peptide sequences of protein coded by 109P1D4 v. 3 (SEQ ID NO : 246) MDLLSGTYIF AVLLACWFH SGAQEKNYTI REEMPENVLI GDLLKDLNLS LIPNKSLTTA 60 MQFKLVYKTG DVPLIRIEED TGEIFTTGAR IDREKLCAGI PRDEHCFYEV EVAILPDEIF 120 RLVKIRFLIE DINDNAPLFP ATVINISIPE NSAINSKYTL PAAVDPDVGI NGVQNYELIK 180 SQNIFGLDVI ETPEGDKMPQ LIVQKELDRE EKDTYVMKVK VEDGGFPQRS STAILQVSVT 240 DTNDNHPVFK ETEIEVSIPE NAPVGTSVTQ LHATDADIGE NAKIHFSFSN LVSNIARRLF 300 HLNATTGLIT IKEPLDREET PNHKLLVLAS DGGLMPARAM VLVNVTDVND NVPSIDIRYI 360 VNPVNDTVVL SENIPLNTKI ALITVTDKDA DHNGRVTCFT DHEIPFRLRP VFSNQFLLET 420 AAYLDYESTK EYAIKLLAAD AGKPPLNQSA MLFIKVKDEN DNAPVFTQSF VTVSIPENNS 480 PGIQLTKVSA MDADSGPNAK INYLLGPDAP PEFSLDCRTG MLTWKKLDR EKEDKYLFTI 540 LAKDNGVPPL TSNVTVFVSI IDQNDNSPVF THNEYNFYVP ENLPRHGTVG LITVTDPDYG 600 DNSAVTLSIL DENDDFTIDS QTGVIRPNIS FDREKQESYT FYVKAEDGGR VSRSSSAKVT 660 INVVDVNDNK PVFIVPPSNC SYELVLPSTN PGTWFQVIA VDNDTGMNAE VRYSIVGGNT 720 RDLFAIDQET GNITLMEKCD VTDLGLHRVL VKANDLGQPD SLFSWIVNL FVNESVTNAT 780 LINELVRKST EAPVTPNTEI ADVSSPTSDY VKILVAAVAG TITVVVVIFI TAVVRCRQAP 840 HLKAAQKNKQ NSEWATPNPE NRQMIMMKKK KKKKKHSPKN LLLNFVTIEE TKADDVDSDG 900 NRVTLDLPID LEEQTMGKYN WVTTPTTFKP DSPDLARHYK SASPQPAFQI QPETPLNSKH 960 HIIQELPLDN TFVACDSISK CSSSSSDPYS VSDCGYPVTT FEVPVSVHTR PPMKEVVRSC 1020 TPMKESTTME IWIHPQPQRK SEGKVAGKSQ RRVTFHLPEG SQESSSDGGL GDHDAGSLTS 1080 TSHGLPLGYP QEEYFDRATP SNRTEGDGNS DPESTFIPGL KKAAEITVQP TVEEASDNCT 1140 QECLIYGHSD ACWMPASLDH SSSSQAQASA LCHSPPLSQA STQHHSPRVT QTIALCHSPP 1200 VTQTIALCHS PPPIQVSALH HSPPLVQATA LHHSPPSAQA SALCYSPPLA QAAAISHSSP 1260 LPQVIALHRS QAQSSVSLQQ GWVQGADGLC SVDQGVQGSA TSQFYTMSER LHPSDDSIKV 1320 IPLTTFTPRQ QARPSRGDSP IMEEHPL 1347 Table LV (b). Amino acid sequence alignment of 109P1 D4 v. 1 (SEQ ID NO : 247) and 109P1D4 v. 3 (SEQ ID NO : 248) Score = 2005 bits (5195), Expect = O. Oldentities = 1011/1011 (100%), Positives = 1011/1011 (100%) V. 1 : 1 MDLLSGTYIFAVLLACVVFHSGAQEKNYTIREEMPENVLIGDLLKDLNLSLIPNKSLTTA 60 MDLLSGTYIFAVLLACVVFHSGAQEKNYTIREEMPENVLIGDLLKDLNLSLIPNKSLTTA V. 3 : 1 MDLLSGTYIFAVLLACWFHSGAQEKNYTIREEMPENVLIGDLLKDLNLSLIPNKSLTTA 60 V. 1 : 61 MQFKLVYKTGDVPLIRIEEDTGEIFTTGARIDREKLCAGIPRDEHCFYEVEVAILPDEIF 120 MQFKLVYKTGDVPLIRIEEDTGEIFTTGARIDREKLCAGIPRDEHCFYEVEVA ILPDEIF V. 3 : 61 MQFKLVYKTGDVPLIRIEEDTGEIFTTGARIDREKLCAGIPRDEHCFYEVEVAILPDEIF 120 V. 1 : 121 RLVKIRFLIEDINDNAPLFPATVINISIPENSAINSKYTLPAAVDPDVGINGVQNYELIK 180 RLVKIRFLIEDINDNAPLFPATVINISIPENSAINSKYTLPAAVDPDVGINGVQNYELIK V. 3 : 121 RLVKIRFLIEDINDNAPLFPATVINISIPENSAINSKYTLPAAVDPDVGINGVQNYELIK 180 V. 1 : 81 SQNIFGLDVIETPEGDKMPQLIVQKELDREEKDTYVMKVKVEDGGFPQRSSTAILQVSVT 240 SQNIFGLDVIETPEGDKMPQLIVQKELDREEKDTYVMKVKVEDGGFPQRSSTAILQVSVT V. 3 : 181 SQNIFGLDVIETPEGDKMPQLIVQKELDREEKDTYVMKVKVEDGGFPQRSSTAILQVSVT 240 V. 1 : 241 DTNDNHPVFKETEIEVSIPENAPVGTSVTQLHATDADIGENAKIHFSFSNLVSNIARRLF 300 DTNDNHPVFKETEIEVSIPENAPVGTSVTQLHATDADIGENAKIHFSFSNLVSNIARRLF V. 3 : 241 DTNDNHPVFKETEIEVSIPENAPVGTSVTQLHATDADIGENAKIHFSFSNLVSNIARRLF 300 V. 1 : 301 HLNATTGLITIKEPLDREETPNHKLLVLASDGGLMPARAMVLVNVTDVNDNVPSIDIRYI 360 HLNATTGLITIKEPLDREETPNHKLLVLASDGGLMPARAMVLVNVTDVNDNVPSIDIRYI V. 3 : 301 HLNATTGLITIKEPLDREETPNHKLLVLASDGGLMPARAMVLVNVTDVNDNVPSIDIRYI 360 V. 1 : 361 VNPVNDTWLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLET 420 VNPVNDTWLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLET V. 3 : 361 VNPVNDTWLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLET 420 V. 1 : 421 AAYLDYESTKEYAIKLLAADAGKPPLNQSAMLFIKVKDENDNAPVFTQSFVTVSIPENNS 480 AAYLDYESTKEYAIKLLAADAGKPPLNQSAMLFIKVKDENDNAPVFTQSFVTVSIPENNS V. 3 : 421 AAYLDYESTKEYAIKLLAADAGKPPLNQSAMLFIKVKDENDNAPVFTQSFVTVSIPENNS 480 V. 1 : 481 PGIQLTKVSAMDADSGPNAKINYLLGPDAPPEFSLDCRTGMLTVVKKLDREKEDKYLFTI 540 PGIQLTKVSAMDADSGPNAKINYLLGPDAPPEFSLDCRTGMLTWKKLDREKEDKYLFTI V. 3 : 481 PGIQLTKVSAMDADSGPNAKINYLLGPDAPPEFSLDCRTGMLTVVKKLDREKEDKYLFTI 540 V. 1 : 541 LAKDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEYNFYVPENLPRHGTVGLITVTDPDYG 600 LAKDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEYNFYVPENLPRHGTVGLITVTDPDYG V. 3 : 541 LAKDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEYNFYVPENLPRHGTVGLITVTDPDYG 600 V. 1 : 601 DNSAVTLSILDENDDFTIDSQTGVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVT 660 DNSAVTLSILDENDDFTIDSQTGVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVT V. 3 : 601 DNSAVTLSILDENDDFTIDSQTGVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVT 660 V. 1 : 661 INWDVNDNKPVFIVPPSNCSYELVLPSTNPGTWFQVIAVDNDTGMNAEVRYSIVGGNT 720 INVVDVNDNKPVFIVPPSNCSYELVLPSTNPGTWFQVIAVDNDTGMNAEVRYSIVGGNT V. 3 : 661 INVVDVNDNKPVFIVPPSNCSYELVLPSTNPGTWFQVIAVDNDTGMNAEVRYSIVGGNT 720 V. 1 : 721 RDLFAIDQETGNITLMEKCDVTDLGLHRVLVKANDLGQPDSLFSWIVNLFVNESVTNAT 780 RDLFAIDQETGNITLMEKCDVTDLGLHRVLVKANDLGQPDSLFSWIVNLFVNESVTNAT V. 3 : 721 RDLFAIDQETGNITLMEKCDVTDLGLHRVLVKANDLGQPDSLFSWIVNLFVNESVTNAT 780 V. 1 : 781 LINELVRKSTEAPVTPNTEIADVSSPTSDYVKILVAAVAGTITVVVVIFITAVVRCRQAP 840 LINELVRKSTEAPVTPNTEIADVSSPTSDYVKILVAAVAGTITVVWIFITAWRCRQAP V. 3 : 781 LINELVRKSTEAPVTPNTEIADVSSPTSDYVKILVAAVAGTITVWVIFITAVVRCRQAP 840 V. 1 : 841 HLKAAQKNKQNSEWATPNPENRQMIMMKKKKKKKKHSPKNLLLNFVTIEETKADDVDSDG 900 Table LII (c). Nucleotide sequence of transcript variant 109P1 D4 v. 4 (SEQ ID NO : 249) ctggtggtcc agtacctcca aagatatgga atacactcct gaaatatcct gaaaactttt 60 ttttttcaga atcctttaat aagcagttat gtcaatctga aagttgctta cttgtacttt 120 atattaatag ctattcttgt ttttcttatc caaagaaaaa tcctctaatc cccttttcac 180 atgatagttg ttaccatgtt taggcattag tcacatcaac ccctctcctc tcccaaactt 240 ctcttcttca aatcaaactt tattagtccc tcctttataa tgattccttg cctcgtttta 300 tccagatcaa ttttttttca ctttgatgcc cagagctgaa gaaatggact actgtataaa 360 ttattcattg ccaagagaat aattgcattt taaacccata ttataacaaa gaataatgat 420 tatattttgt gatttgtaac aaataccctt tattttccct taactattga attaaatatt 480 ttaattattt gtattctctt taactatctt ggtatattaa agtattatct tttatatatt 540 tatcaatggt ggacactttt ataggtactc tgtgtcattt ttgatactgt aggtatctta 600 tttcatttat ctttattctt aatgtacgaa ttcataatat ttgattcaga acaaatttat 660 cactaattaa cagagtgtca attatgctaa catctcattt actgatttta atttaaaaca 720 gtttttgtta acatgcatgt ttagggttgg cttcttaata atttcttctt cctcttctct 780 ctctcctctt cttttggtca gtgttgtgcg ggttaataca acaaactgta acaagtgtac 840 ctggtatgga cttgttgtcc gggacgtaca ttttcgcggt cctgctagca tgcgtggtgt 900 tccactctgg cgcccaggag aaaaactaca ccatccgaga agaaatgcca gaaaacgtcc 960 tgataggcga cttgttgaaa gaccttaact tgtcgctgat tccaaacaag tccttgacaa 1020 ctgctatgca gttcaagcta gtgtacaaga ccggagatgt gccactgatt cgaattgaag 1080 aggatactgg tgagatcttc actactggcg ctcgcattga tcgtgagaaa ttatgtgctg 1140 gtatcccaag ggatgagcat tgcttttatg aagtggaggt tgccattttg ccggatgaaa 1200 tatttagact ggttaagata cgttttctga tagaagatat aaatgataat gcaccattgt 1260 tcccagcaac agttatcaac atatcaattc cagagaactc ggctataaac tctaaatata 1320 ctctcccagc ggctgttgat cctgacgtag gaataaacgg agttcaaaac tacgaactaa 1380 ttaagagtca aaacattttt ggcctcgatg tcattgaaac accagaagga gacaagatgc 1440 cacaactgat tgttcaaaag gagttagata gggaagagaa ggatacctac gtgatgaaag 1500 taaaggttga agatggtggc tttcctcaaa gatccagtac tgctattttg caagtgagtg 1560 ttactgatac aaatgacaac cacccagtct ttaaggagac agagattgaa gtcagtatac 1620 cagaaaatgc tcctgtaggc acttcagtga cacagctcca tgccacagat gctgacatag 1680 gtgaaaatgc caagatccac ttctctttca gcaatctagt ctccaacatt gccaggagat 1740 tatttcacct caatgccacc actggactta tcacaatcaa agaaccactg gatagggaag 1800 aaacaccaaa ccacaagtta ctggttttgg caagtgatgg tggattgatg ccagcaagag 1860 caatggtgct ggtaaatgtt acagatgtca atgataatgt cccatccatt gacataagat 1920 acatcgtcaa tcctgtcaat gacacagttg ttctttcaga aaatattcca ctcaacacca 1980 aaattgctct cataactgtg acggataagg atgcggacca taatggcagg gtgacatgct 2040 tcacagatca tgaaatccct ttcagattaa ggccagtatt cagtaatcag ttcctcctgg 2100 agactgcagc atatcttgac tatgagtcca caaaagaata tgccattaaa ttactggctg 2160 cagatgctgg caaacctcct ttgaatcagt cagcaatgct cttcatcaaa gtgaaagatg 2220 aaaatgacaa tgctccagtt ttcacccagt ctttcgtaac tgtttctatt cctgagaata 2280 actctcctgg catccagttg acgaaagtaa gtgcaatgga tgcagacagt gggcctaatg 2340 ctaagatcaa ttacctgcta ggccctgatg ctccacctga attcagcctg gattgtcgta 2400 caggcatgct gactgtagtg aagaaactag atagagaaaa agaggataaa tatttattca 2460 caattctggc aaaagataac ggggtaccac ccttaaccag caatgtcaca gtctttgtaa 2520 gcattattga tcagaatgac aatagcccag ttttcactca caatgaatac aacttctatg 2580 tcccagaaaa ccttccaagg catggtacag taggactaat cactgtaact gatcctgatt 2640 atggagacaa ttctgcagtt acgctctcca ttttagatga gaatgatgac ttcaccattg 2700 attcacaaac tggtgtcatc cgaccaaata tttcatttga tagagaaaaa caagaatctt 2760 acactttcta tgtaaaggct gaggatggtg gtagagtatc acgttcttca agtgccaaag 2820 taaccataaa tgtggttgat gtcaatgaca acaaaccagt tttcattgtc cctccttcca 2880 actgttctta tgaattggtt ctaccgtcca ctaatccagg cacagtggtc tttcaggtaa 2940 ttgctgttga caatgacact ggcatgaatg cagaggttcg ttacagcatt gtaggaggaa 3000 acacaagaga tctgtttgca atcgaccaag aaacaggcaa cataacattg atggagaaat 3060 gtgatgttac agaccttggt ttacacagag tgttggtcaa agctaatgac ttaggacagc 3120 ctgattctct cttcagtgtt gtaattgtca atctgttcgt gaatgagtcg gtgaccaatg 3180 ctacactgat taatgaactg gtgcgcaaaa gcactgaagc accagtgacc ccaaatactg 3240 agatagctga tgtatcctca ccaactagtg actatgtcaa gatcctggtt gcagctgttg 3300 ctggcaccat aactgtcgtt gtagttattt tcatcactgc tgtagtaaga tgtcgccagg 3360 caccacacct taaggctgct cagaaaaaca agcagaattc tgaatgggct accccaaacc 3420 cagaaaacag gcagatgata atgatgaaga aaaagaaaaa gaagaagaag cattccccta 3480 agaacttgct gcttaatttt gtcactattg aagaaactaa ggcagatgat gttgacagtg 3540 atggaaacag agtcacacta gaccttccta ttgatctaga agagcaaaca atgggaaagt 3600 acaattgggt aactacacct actactttca agcccgacag ccctgatttg gcccgacact 3660 acaaatctgc ctctccacag cctgccttcc aaattcagcc tgaaactccc ctgaattcga 3720 agcaccacat catccaagaa ctgcctctcg ataacacctt tgtggcctgt gactctatct 3780 ccaagtgttc ctcaagcagt tcagatccct acagcgtttc tgactgtggc tatccagtga 3840 cgaccttcga ggtacctgtg tccgtacaca ccagaccgcc aatgaaggag gttgtgcgat 3900 cttgcacccc catgaaagag tctacaacta tggagatctg gattcatccc caaccacagt 3960 cccagcggcg tgtcacattt cacctgccag aaggctctca ggaaagcagc agtgatggtg 4020 gactgggaga ccatgatgca ggcagcctta ccagcacatc tcatggcctg ccccttggct 4080 atcctcagga ggagtacttt gatcgtgcta cacccagcaa tcgcactgaa ggggatggca 4140 actccgatcc tgaatctact ttcatacctg gactaaagaa agctgcagaa ataactgttc 4200 aaccaactgt ggaagaggcc tctgacaact gcactcaaga atgtctcatc tatggccatt 4260 ctgatgcctg ctggatgccg gcatctctgg atcattccag ctcttcgcaa gcacaggcct 4320 ctgctctatg ccacagccca ccactgtcac aggcctctac tcagcaccac agcccacgag 4380 tgacacagac cattgctctc tgccacagcc ctccagtgac acagaccatc gcattgtgcc 4440 acagcccacc accgatacag gtgtctgctc tccaccacag tcctcctcta gtgcaggcta 4500 ctgcacttca ccacagccca ccatcagcac aggcctcagc cctctgctac agccctcctt 4560 tagcacaggc tgctgcaatc agccacagct ctcctctgcc acaggttatt gccctccatc 4620 gtagtcaggc ccaatcatca gtcagtttgc agcaaggttg ggtgcaaggt gctgatgggc 4680 tatgctctgt tgatcaggga gtgcaaggta gtgcaacatc tcagttttac accatgtctg 4740 aaagacttca tcccagtgat gattcaatta aagtcattcc tttgacaacc ttcactccac 4800 gccaacaggc cagaccgtcc agaggtgatt cccccattat ggaagaacat cccttgtaaa 4860 gctaaaatag ttacttcaaa ttttcagaaa agatgtatat agtcaaaatt taagatacaa 4920 ttccaatgag tattctgatt atcagatttg taaataacta tgtaaataga aacagatacc 4980 agaataaatc tacagctaga cccttagtca atagttaacc aaaaaattgc aatttgttta 5040 attcagaatg tgtatttaaa aagaaaagga atttaacaat ttgcatcccc ttgtacagta 5100 aggcttatca tgacagagcg cactatttct gatgtacagt attttttgtt gtttttatca 5160 tcatgtgcaa tattactgat ttgtttccat gctgattgtg tggaaccagt atgtagcaaa 5220 tggaaagcct agaaatatct tattttctaa gtttaccttt agtttaccta aacttttgtt 5280 cagataacgt taaaaggtat acgtactcta gccttttttt gggctttctt tttgattttt 5340 gtttgttgtt ttcagttttt ttgttgttgt tagtgagtct cccttcaaaa tacgcagtag 5400 gtagtgtaaa tactgcttgt ttgtgtctct ctgctgtcat gttttctacc ttattccaat 5460 actatattgt tgataaaatt tgtatataca ttttcaataa agaatatgta taaactgtac 5520 agatctagat ctacaaccta tttctctact ctttagtaga gttcgagaca cagaagtgca 5580 ataactgccc taattaagca actatttgtt aaaaagggcc tctttttact ttaatagttt 5640 agtgtaaagt acatcagaaa taaagctgta tctgccattt taagcctgta gtccattatt 5700 acttgggtct ttacttctgg gaatttgtat gtaacagcct agaaaattaa aaggaggtgg 5760 atgcatccaa agcacgagtc acttaaaata tcgacggtaa actactattt tgtagagaaa 5820 ctcaggaaga tttaaatgtt gatttgacag ctcaataggc tgttaccaaa gggtgttcag 5880 taaaaataac aaatacatgt aactgtagat aaaaccatat actaaatcta taagactaag 5940 ggatttttgt tattctagct caacttactg aagaaaacca ctaataacaa caagaatatc 6000 aggaaggaac ttttcaagaa atgtaattat aaatctacat caaacagaat tttaaggaaa 6060 aatgcagagg gagaaataag gcacatgact gcttcttgca gtcaacaaga aataccaata 6120 acacacacag aacaaaaacc atcaaaatct catatatgaa ataaaatata ttcttctaag 6180 caaagaaaca gtactattca tagaaaacat tagttttctt ctgttgtctg ttatttcctt 6240 cttgtatcct cttaactggc cattatcttg tatgtgcaca ttttataaat gtacagaaac 6300 atcaccaact taattttctt ccatagcaaa actgagaaaa taccttgttt cagtataaca 6360 ctaaaccaag agacaattga tgtttaatgg gggcggttgg ggtggggggg ggagtcaata 6420 tctcctattg attaacttag acatagattt tgtaatgtat aacttgatat ttaatttatg 6480 attaaactgt gtgtaaattt tgtaacataa actgtggtaa ttgcataatt tcattggtga 6540 ggatttccac tgaatattga gaaagtttct tttcatgtgc ccagcaggtt aagtagcgtt 6600 ttcagaatat acattattcc catccattgt aaagttcctt aagtcatatt tgactgggcg 6660 tgcagaataa cttcttaact tttaactatc agagtttgat taataaaatt aattaatgtt 6720 ttttctcctt cgtgttgtta atgttccaag ggatttggag catactggtt ttccaggtgc 6780 atgtgaatcc cgaaggactg atgatatttg aatgtttatt aaattattat catacaaatg 6840 tgttgatatt gtggctattg ttgatgttga aaattttaaa cttggggaag attaagaaaa 6900 gaaccaatag tgacaaaaat cagtgcttcc agtagatttt agaacattct ttgcctcaaa 6960 aaacctgcaa agatgatgtg agattttttc ttgtgtttta attattttca cattttctct 7020 ctgcaaaact ttagttttct gatgatctac acacacacac acacacacac gtgcacacac 7080 acacacattt aaatgatata aaaagaagag gttgaaagat tattaaataa cttatcaggc 7140 atctcaatgg ttactatcta tgttagtgaa aatcaaatag gactcaaagt tggatatttg 7200 ggatttttct tctgacagta taatttattg agttactagg gaggttctta aatcctcata 7260 tctggaaact tgtgacgttt tgacaccttt cctatagatg atataggaat gaaccaatac 7320 gcttttatta ccctttctaa ctctgatttt ataatcagac ttagattgtg tttagaatat 7380 taaatgactg ggcaccctct tcttggtttt taccagagag gctttgaatg gaagcaggct 7440 gagagtagcc aaagaggcaa ggggtattag cccagttatt ctcccctatg ccttccttct 7500 ctttctaagc gtccactagg tctggccttg gaaacctgtt acttctaggg cttcagatct 7560 gatgatatct ttttcatcac attacaagtt atttctctga ctgaatagac agtggtatag 7620 gttgacacag cacacaagtg gctattgtga tgtatgatgt atgtagtcct acaactgcaa 7680 aacgtcttac tgaaccaaca atcaaaaaat ggttctgttt taaaaaggat tttgtttgat 7740 ttgaaattaa aacttcaagc tgaatgactt atatgagaat aatacgttca atcaaagtag 7800 ttattctatt ttgtgtccat attccattag attgtgatta ttaattttct agctatggta 7860 ttactatatc acacttgtga gtatgtattc aaatactaag tatcttatat gctacgtgca 7920 tacacattct tttcttaaac tttacctgtg ttttaactaa tattgtgtca gtgtattaaa 7980 aattagcttt tacatatgat atctacaatg taataaattt agagagtaat tttgtgtatt 8040 cttatttact taacatttta cttttaatta tgtaaatttg gttagaaaat aataataaat 8100 ggttagtgct attgtgtaat ggtagcagtt acaaagagcc tctgccttcc caaactaata 8160 tttatcacac atggtcatta aatgggaaaa aaatagacta aacaaatcac aaattgttca 8220 gttcttaaaa tgtaattatg tcacacacac aaaaaatcct tttcaatcct gagaaaatta 8280 aaggcgtttt actcacatgg ctatttcaac attagttttt tttgtttgtt tctttttcat 8340 ggtattactg aaggtgtgta tactccctaa tacacattta tgaaaatcta cttgtttagg 8400 cttttattta tactcttctg atttatattt tttattataa ttattatttc ttatctttct 8460 tcttttatat tttttggaaa ccaaatttat agttagttta ggtaaacttt ttattatgac 8520 cattagaaac tattttgaat gcttccaact ggctcaattg gccgggaaaa catgggagca 8580 agagaagctg aaatatattt ctgcaagaac ctttctatat tatgtgccaa ttaccacacc 8640 agatcaattt tatgcagagg ccttaaaata ttctttcaca gtagctttct tacactaacc 8700 gtcatgtgct tttagtaaat atgattttta aaagcagttc aagttgacaa cagcagaaac 8760 agtaacaaaa aaatctgctc agaaaaatgt atgtgcacaa ataaaaaaaa ttaatggcaa 8820 ttgtttagtg attgtaagtg atacttttta aagagtaaac tgtgtgaaat ttatactatc 8880 cctgcttaaa atattaagat ttttatgaaa tatgtattta tgtttgtatt gtgggaagat 8940 tcctcctctg tgatatcata cagcatctga aagtgaacag tatcccaaag cagttccaac 9000 catgctttgg aagtaagaag gttgactatt gtatggccaa ggatggcagt atgtaatcca 9060 gaagcaaact tgtattaatt gttctatttc aggttctgta ttgcatgttt tcttattaat 9120 atatattaat aaaagttatg agaaat 9146 Table Lull (c). Nucleotide sequence alignment of 109P1D4 v. 1 (SEQ ID NO : 250) and 109P1D4 v. 4 (SEQ ID NO : 251) Score = 7456 bits (3878), Expect = O. Oldentities = 3878/3878 (100%) Strand = Plus/Plus V. 1 : 1 ctggtggtccagtacctccaaagatatggaatacactcctgaaatatcctgaaaactttt 60 Illlllllllllllllllllllllllllllllllllllllilllllllllllllllllll V. 4 : 1 ctggtggtccagtacctccaaagatatggaatacactcctgaaatatcctgaaaactttt 60 V. 1 : 61 ttttttcagaatcctttaataagcagttatgtcaatctgaaagttgcttacttgtacttt 120 111111111111111111111111111111111111111111111111111111111111 V. 4: 61 ttttttcagaatcctttaataagcagttatgtcaatctgaaagttgcttacttgtacttt 120 V. 1 : 121 atattaatagctattcttgtttttcttatccaaagaaaaatcctctaatccccttttcac 180 111111111111111111111111|11111111111111111111111111111111111 V. 4 : 121 atattaatagctattcttgtttttcttatccaaagaaaaatcctctaatccccttttcac 180 V. 1 : 181 atgatagttgttaccatgtttaggcattagtcacatcaacccctctcctctcccaaactt 240 Illllllllllllllllllllllllllllllllllllllllllllllllllllfllllll V. 4 : 181 atgatagttgttaccatgtttaggcattagtcacatcaacccctctcctctcccaaactt 240 V. 1 : 241 ctcttcttcaaatcaaactttattagtccctcctttataatgattccttgcctcgtttta 300 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 4 : 241 ctcttcttcaaatcaaactttattagtccctcctttataatgattccttgcctcgtttta 300 V. 1 : 301 tccagatcaattttttttcactttgatgcccagagctgaagaaatggactactgtataaa 360 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 4 : 301 tccagatcaattttttttcactttgatgcccagagctgaagaaatggactactgtataaa 360 V. 1 : 361 ttattcattgccaagagaataattgcattttaaacccatattataacaaagaataatgat 420 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 4 : 361 ttattcattgccaagagaataattgcattttaaacccatattataacaaagaataatgat 420 V. 1 : 421 tatattttgtgatttgtaacaaataccctttattttcccttaactattgaattaaatatt 480 Illlilllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 4 : 421 tatattttgtgatttgtaacaaataccctttattttcccttaactattgaattaaatatt 480 V. 1 : 481 ttaattatttgtattctctttaactatcttggtatattaaagtattatcttttatatatt 540 Illlllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 4 : 481 ttaattatttgtattctctttaactatcttggtatattaaagtattatcttttatatatt 540 V. 1 : 541 tatcaatggtggacacttttataggtactctgtgtcatttttgatactgtaggtatctta 600 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII. IIIIIIIIIIIIIIIIIIIIIIII V. 4 : 541 tatcaatggtggacacttttataggtactctgtgtcatttttgatactgtaggtatctta 600 V. 1 : 601 tttcatttatctttattcttaatgtacgaattcataatatttgattcagaacaaatttat 660 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 4 : 601 tttcatttatctttattcttaatgtacgaattcataatatttgattcagaacaaatttat 660 V. 1 : 661 cactaattaacagagtgtcaattatgctaacatctcatttactgattttaatttaaaaca 720 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 4 : 661 cactaattaacagagtgtcaattatgctaacatctcatttactgattttaatttaaaaca 720 V. 1 : 721 gtttttgttaacatgcatgtttagggttggcttcttaataatttcttcttcctcttctct 780 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 4 : 721 gtttttgttaacatgcatgtttagggttggcttcttaataatttcttcttcctcttctct 780 V. 1 : 781 ctctcctcttcttttggtcagtgttgtgcgggttaatacaacaaactgtaacaagtgtac 840 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 4 : 781 ctctcctcttcttttggtcagtgttgtgcgggttaatacaacaaactgtaacaagtgtac 840 V. 1 : 841 ctggtatggacttgttgtccgggacgtacattttcgcggtcctgctagcatgcgtggtgt 900 Illlllllllllllllllllllllllllllllllllllllllllllllllllilllllll V. 4 : 841 ctggtatggacttgttgtccgggacgtacattttcgcggtcctgctagcatgcgtggtgt 900 V. 1 : 901 tccactctggcgcccaggagaaaaactacaccatccgagaagaaatgccagaaaacgtcc 960 IIIlllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 4 : 901 tccactctggcgcccaggagaaaaactacaccatccgagaagaaatgccagaaaacgtcc 960 V. 1 : 961 tgataggcgacttgttgaaagaccttaacttgtcgctgattccaaacaagtccttgacaa 1020 Illlllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 4 : 961 tgataggcgacttgttgaaagaccttaacttgtcgctgattccaaacaagtccttgacaa 1020 V. 1 : 1021 ctgctatgcagttcaagctagtgtacaagaccggagatgtgccactgattcgaattgaag 1080 V. 4 : 1021 ctgctatgcagttcaagctagtgtacaagaccggagatgtgccactgattcgaattgaag 1080 V. 4. 1021 ctgctatgcagttcaagctagtgtacaagaccggagatgtgccactgattcgaattgaag 1080 V. 1 : 1081 aggatactggtgagatcttcactactggcgctcgcattgatcgtgagaaattatgtgctg 1140 11111111111111l111111111111111111111111111111111111111111111 V. 4 : 1081 aggatactggtgagatcttcactactggcgctcgcattgatcgtgagaaattatgtgctg 1140 V. 1 : 1141 gtatcccaagggatgagcattgcttttatgaagtggaggttgccattttgccggatgaaa 1200 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 4 : 1141 gtatcccaagggatgagcattgcttttatgaagtggaggttgccattttgccggatgaaa 1200 V. 1 : 1201 tatttagactggttaagatacgttttctgatagaagatataaatgataatgcaccattgt 1260 Illlllllllllilllllllllllllllllllllllllllllllllllllllllllllll V. 4 : 1201 tatttagactggttaagatacgttttctgatagaagatataaatgataatgcaccattgt 1260 V. 1 : 1261 tcccagcaacagttatcaacatatcaattccagagaactcggctataaactctaaatata 1320 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 4 : 1261 tcccagcaacagttatcaacatatcaattccagagaactcggctataaactctaaatata 1320 V. 1 : 1321 ctctcccagcggctgttgatcctgacgtaggaataaacggagttcaaaactacgaactaa 1380 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 4 : 1321 ctctcccagcggctgttgatcctgacgtaggaataaacggagttcaaaactacgaactaa 1380 V. 1 : 1381 ttaagagtcaaaacatttttggcctcgatgtcattgaaacaccagaaggagacaagatgc 1440 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIilll lllllll V. 4 : 1381 ttaagagtcaaaacatttttggcctcgatgtcattgaaacaccagaaggagacaagatgc 1440 V. 1 : 1441 cacaactgattgttcaaaaggagttagatagggaagagaaggatacctacgtgatgaaag 1500 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 4 : 1441 cacaactgattgttcaaaaggagttagatagggaagagaaggatacctacgtgatgaaag 1500 V. 1 : 1501 taaaggttgaagatggtggctttcctcaaagatccagtactgctattttgcaagtgagtg 1560 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 4 : 1501 taaaggttgaagatggtggctttcctcaaagatccagtactgctattttgcaagtgagtg 1560 V. 1 : 1561 ttactgatacaaatgacaaccacccagtctttaaggagacagagattgaagtcagtatac 1620 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 4 : 1561 ttactgatacaaatgacaaccacccagtctttaaggagacagagattgaagtcagtatac 1620 V. 1 : 1621 cagaaaatgctcctgtaggcacttcagtgacacagctccatgccacagatgctgacatag 1680 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 4 : 1621 cagaaaatgctcctgtaggcacttcagtgacacagctccatgccacagatgctgacatag 1680 V. 1 : 1681 gtgaaaatgccaagatccacttctctttcagcaatctagtctccaacattgccaggagat 1740 11111111111111111111|111111111111111111111111111111111111111 V. 4 : 1681 gtgaaaatgccaagatccacttctctttcagcaatctagtctccaacattgccaggagat 1740 V. 1 : 1741 tatttcacctcaatgccaccactggacttatcacaatcaaagaaccactggatagggaag 1800 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 4 : 1741 tatttcacctcaatgccaccactggacttatcacaatcaaagaaccactggatagggaag 1800 V. 1 : 1801 aaacaccaaaccacaagttactggttttggcaagtgatggtggattgatgccagcaagag 1860 Illlllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 4 : 1801 aaacaccaaaccacaagttactggttttggcaagtgatggtggattgatgccagcaagag 1860 V. 1 : 1861 caatggtgctggtaaatgttacagatgtcaatgataatgtcccatccattgacataagat 1920 111111111111111111111111111111111111111111111111111111111111 V. 4 : 861 caatggtgctggtaaatgttacagatgtcaatgataatgtcccatccattgacataagat 1920 V. 1 : 1921 acatcgtcaatcctgtcaatgacacagttgttctttcagaaaatattccactcaacacca 1980 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 4 : 1921 acatcgtcaatcctgtcaatgacacagttgttctttcagaaaatattccactcaacacca 1980 V. 1 : 1981 aaattgctctcataactgtgacggataaggatgcggaccataatggcagggtgacatgct 2040 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 4 : 1981 aaattgctctcataactgtgacggataaggatgcggaccataatggcagggtgacatgct 2040 V. 1 : 2041 tcacagatcatgaaatccctttcagattaaggccagtattcagtaatcagttcctcctgg 2100 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 4 : 2041 tcacagatcatgaaatccctttcagattaaggccagtattcagtaatcagttcctcctgg 2100 V. 1 : 2101 agactgcagcatatcttgactatgagtccacaaaagaatatgccattaaattactggctg 2160 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 4 : 2101 agactgcagcatatcttgactatgagtccacaaaagaatatgccattaaattactggctg 2160 V. 1 : 2161 cagatgctggcaaacctcctttgaatcagtcagcaatgctcttcatcaaagtgaaagatg 2220 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 4 : 2161 cagatgctggcaaacctcctttgaatcagtcagcaatgctcttcatcaaagtgaaagatg 2220 V. 1 : 2221 aaaatgacaatgctccagttttcacccagtctttcgtaactgtttctattcctgagaata 2280 IIIlllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 4 : 2221 aaaatgacaatgctccagttttcacccagtctttcgtaactgtttctattcctgagaata 2280 V. 1 : 2281 actctcctggcatccagttgacgaaagtaagtgcaatggatgcagacagtgggcctaatg 2340 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 4 : 2281 actctcctggcatccagttgacgaaagtaagtgcaatggatgcagacagtgggcctaatg 2340 V. 1 : 2341 ctaagatcaattacctgctaggccctgatgctccacctgaattcagcctggattgtcgta 2400 Illllllllllllllllllllillllllllllllllllllllllllllllllllllllll V. 4 : 2341 ctaagatcaattacctgctaggccctgatgctccacctgaattcagcctggattgtcgta 2400 V. 1 : 2401 caggcatgctgactgtagtgaagaaactagatagagaaaaagaggataaatatttattca 2460 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIilllllllll V. 4 : 2401 caggcatgctgactgtagtgaagaaactagatagagaaaaagaggataaatatttattca 2460 V. 1 : 2461 caattctggcaaaagataacggggtaccacccttaaccagcaatgtcacagtctttgtaa 2520 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 4 : 2461 caattctggcaaaagataacggggtaccacccttaaccagcaatgtcacagtctttgtaa 2520 V. 1 : 2521 gcattattgatcagaatgacaatagcccagttttcactcacaatgaatacaacttctatg 2580 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 4 : 2521 gcattattgatcagaatgacaatagcccagttttcactcacaatgaatacaacttctatg 2580 V. 1 : 2581 tcccagaaaaccttccaaggcatggtacagtaggactaatcactgtaactgatcctgatt 2640 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 4 : 2581 tcccagaaaaccttccaaggcatggtacagtaggactaatcactgtaactgatcctgatt 2640 V. 1 : 2641 atggagacaattctgcagttacgctctccattttagatgagaatgatgacttcaccattg 2700 Illllllllllllllllllllllllllllllllllllllllllllllllllidlllllll V. 4 : 2641 atggagacaattctgcagttacgctctccattttagatgagaatgatgacttcaccattg 2700 V. 1 : 2701 attcacaaactggtgtcatccgaccaaatatttcatttgatagagaaaaacaagaatctt 2760 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 4 : 2701 attcacaaactggtgtcatccgaccaaatatttcatttgatagagaaaaacaagaatctt 2760 V. 1 : 2761 acactttctatgtaaaggctgaggatggtggtagagtatcacgttcttcaagtgccaaag 2820 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 4 : 2761 acactttctatgtaaaggctgaggatggtggtagagtatcacgttcttcaagtgccaaag 2820 V. 1 : 2821 taaccataaatgtggttgatgtcaatgacaacaaaccagttttcattgtccctccttcca 2880 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 4 : 2821 taaccataaatgtggttgatgtcaatgacaacaaaccagttttcattgtccctccttcca 2880 V. 1 : 2881 actgttcttatgaattggttctaccgtccactaatccaggcacagtggtctttcaggtaa 2940 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 4 : 2881 actgttcttatgaattggttctaccgtccactaatccaggcacagtggtctttcaggtaa 2940 V. 1 : 2941 ttgctgttgacaatgacactggcatgaatgcagaggttcgttacagcattgtaggaggaa 3000 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 4 : 2941 ttgctgttgacaatgacactggcatgaatgcagaggttcgttacagcattgtaggaggaa 3000 V. 1 : 3001 acacaagagatctgtttgcaatcgaccaagaaacaggcaacataacattgatggagaaat 3060 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 4 : 3001 acacaagagatctgtttgcaatcgaccaagaaacaggcaacataacattgatggagaaat 3060 V. 1 : 3061 gtgatgttacagaccttggtttacacagagtgttggtcaaagctaatgacttaggacagc 3120 IIIIIIIIIIIIIIIIilllllllllllllllllllllllllllllllllllllllllll V. 4 : 3061 gtgatgttacagaccttggtttacacagagtgttggtcaaagctaatgacttaggacagc 3120 V. 1 : 3121 ctgattctctcttcagtgttgtaattgtcaatctgttcgtgaatgagtcggtgaccaatg 3180 11111111111111111111111111111111111111111111111111111111|111 V. 4 : 3121 ctgattctctcttcagtgttgtaattgtcaatctgttcgtgaatgagtcggtgaccaatg 3180 V. 1 : 3181 ctacactgattaatgaactggtgcgcaaaagcactgaagcaccagtgaccccaaatactg 3240 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 4 : 3181 ctacactgattaatgaactggtgcgcaaaagcactgaagcaccagtgaccccaaatactg 3240 V. 1 : 3241 agatagctgatgtatcctcaccaactagtgactatgtcaagatcctggttgcagctgttg 3300 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 4 : 3241 agatagctgatgtatcctcaccaactagtgactatgtcaagatcctggttgcagctgttg 3300 V. 1 : 3301 ctggcaccataactgtcgttgtagttattttcatcactgctgtagtaagatgtcgccagg 3360 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 4 : 3301 ctggcaccataactgtcgttgtagttattttcatcactgctgtagtaagatgtcgccagg 3360 V. 1 : 3361 caccacaccttaaggctgctcagaaaaacaagcagaattctgaatgggctaccccaaacc 3420 Illlllllllllllllllilllllllllllllllllllllllllllllllllllllllll V. 4 : 3361 caccacaccttaaggctgctcagaaaaacaagcagaattctgaatgggctaccccaaacc 3420 V. 1 : 3421 cagaaaacaggcagatgataatgatgaagaaaaagaaaaagaagaagaagcattccccta 3480 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 4 : 3421 cagaaaacaggcagatgataatgatgaagaaaaagaaaaagaagaagaagcattccccta 3480 V. 1 : 3481 agaacttgctgcttaattttgtcactattgaagaaactaaggcagatgatgttgacagtg 3540 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 4 : 3481 agaacttgctgcttaattttgtcactattgaagaaactaaggcagatgatgttgacagtg 3540 V. 1 : 3541 atggaaacagagtcacactagaccttcctattgatctagaagagcaaacaatgggaaagt 3600 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 4 : 3541 atggaaacagagtcacactagaccttcctattgatctagaagagcaaacaatgggaaagt 3600 V. 1 : 3601 acaattgggtaactacacctactactttcaagcccgacagccctgatttggcccgacact 3660 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 4 : 3601 acaattgggtaactacacctactactttcaagcccgacagccctgatttggcccgacact 3660 V. 1 : 3661 acaaatctgcctctccacagcctgccttccaaattcagcctgaaactcccctgaattcga 3720 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 4 : 3661 acaaatctgcctctccacagcctgccttccaaattcagcctgaaactcccctgaattcga 3720 V. 1 : 3721 agcaccacatcatccaagaactgcctctcgataacacctttgtggcctgtgactctatct 3780 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 4 : 3721 agcaccacatcatccaagaactgcctctcgataacacctttgtggcctgtgactctatct 3780 V. 1 : 3781 ccaagtgttcctcaagcagttcagatccctacagcgtttctgactgtggctatccagtga 3840 Illlllllllllllllllllllllllllllllllllllllllilllllllllllllllll V. 4 : 3781 ccaagtgttcctcaagcagttcagatccctacagcgtttctgactgtggctatccagtga 3840 V. 1 : 3841 cgaccttcgaggtacctgtgtccgtacacaccagaccg 3878 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 4 : 3841 cgaccttcgaggtacctgtgtccgtacacaccagaccg 3878 Table LIV (c). Peptide sequences of protein coded by 109P1D4 v. 4 (SEQ ID NO : 252) MDLLSGTYIF AVLLACWFH SGAQEKNYTI REEMPENVLI GDLLKDLNLS LIPNKSLTTA 60 MQFKLVYKTG DVPLIRIEED TGEIFTTGAR IDREKLCAGI PRDEHCFYEV EVAILPDEIF 120 RLVKIRFLIE DINDNAPLFP ATVINISIPE NSAINSKYTL PAAVDPDVGI NGVQNYELIK 180 SQNIFGLDVI ETPEGDKMPQ LIVQKELDRE EKDTYVMKVK VEDGGFPQRS STAILQVSVT 240 DTNDNHPVFK ETEIEVSIPE NAPVGTSVTQ LHATDADIGE NAKIHFSFSN LVSNIARRLF 300 HLNATTGLIT IKEPLDREET PNHKLLVLAS DGGLMPARAM VLVNVTDVND NVPSIDIRYI 360 VNPVNDTWL SENIPLNTKI ALITVTDKDA DHNGRVTCFT DHEIPFRLRP VFSNQFLLET 420 AAYLDYESTK EYAIKLLAAD AGKPPLNQSA MLFIKVKDEN DNAPVFTQSF VTVSIPENNS 480 PGIQLTKVSA MDADSGPNAK INYLLGPDAP PEFSLDCRTG MLTVVKKLDR EKEDKYLFTI 540 LAKDNGVPPL TSNVTVFVSI IDQNDNSPVF THNEYNFYVP ENLPRHGTVG LITVTDPDYG 600 DNSAVTLSIL DENDDFTIDS QTGVIRPNIS FDREKQESYT FYVKAEDGGR VSRSSSAKVT 660 INVVDVNDNK PVFIVPPSNC SYELVLPSTN PGTVVFQVIA VDNDTGMNAE VRYSIVGGNT 720 RDLFAIDQET GNITLMEKCD VTDLGLHRVL VKANDLGQPD SLFSVVIVNL FVNESVTNAT 780 LINELVRKST EAPVTPNTEI ADVSSPTSDY VKILVAAVAG TITVVVVIFI TAVVRCRQAP 840 HLKAAQKNKQ NSEWATPNPE NRQMIMMKKK KKKKKHSPKN LLLNFVTIEE TKADDVDSDG 900 NRVTLDLPID LEEQTMGKYN WVTTPTTFKP DSPDLARHYK SASPQPAFQI QPETPLNSKH 960 HIIQELPLDN TFVACDSISK CSSSSSDPYS VSDCGYPVTT FEVPVSVHTR PPMKEWRSC 1020 TPMKESTTME IWIHPQPQSQ RRVTFHLPEG SQESSSDGGL GDHDAGSLTS TSHGLPLGYP 1080 QEEYFDRATP SNRTEGDGNS DPESTFIPGL KKAAEITVQP TVEEASDNCT QECLIYGHSD 1140 ACWMPASLDH SSSSQAQASA LCHSPPLSQA STQHHSPRVT QTIALCHSPP VTQTIALCHS 1200 PPPIQVSALH HSPPLVQATA LHHSPPSAQA SALCYSPPLA QAAAISHSSP LPQVIALHRS 1260 QAQSSVSLQQ GWVQGADGLC SVDQGVQGSA TSQFYTMSER LHPSDDSIKV IPLTTFTPRQ 1320 QARPSRGDSP IMEEHPL 1337 Table LV (c). Amino acid sequence alignment of 109P1 D4 v. 1 (SEQ ID NO : 253) and 109P1D4 v. 4 (SEQ ID NO : 254) Score = 2005 bits (5195), Expect = O. Oldentities = 1011/1011 (100%), Positives = 1011/1011 (100%) V. I : 1 MDLLSGTYIFAVLLACWFHSGAQEKNYTIREEMPENVLIGDLLKDLNLSLIPNKSLTTA 60 MDLLSGTYIFAVLLACWFHSGAQEKNYTIREEMPENVLIGDLLKDLNLSLIPNKSLTTA V. 4 : 1 MDLLSGTYIFAVLLACVVFHSGAQEKNYTIREEMPENVLIGDLLKDLNLSLIPNKSLTTA 60 V. 1 : 61 MQFKLVYKTGDVPLIRIEEDTGEIFTTGARIDREKLCAGIPRDEHCFYEVEVAILPDEIF 120 MQFKLVYKTGDVPLIRIEEDTGEIFTTGARIDREKLCAGIPRDEHCFYEVEVAILPDEIF V. 4 : 61 MQFKLVYKTGDVPLIRIEEDTGEIFTTGARIDREKLCAGIPRDEHCFYEVEVAILPDEIF 120 V. 1 : 121 RLVKIRFLIEDINDNAPLFPATVINISIPENSAINSKYTLPAAVDPDVGINGVQNYELIK 180 RLVKIRFLIEDINDNAPLFPATVINISIPENSAINSKYTLPAAVDPDVGINGVQNYELIK V. 4 : 121 RLVKIRFLIEDINDNAPLFPATVINISIPENSAINSKYTLPAAVDPDVGINGVQNYELIK 180 V. 1 : 181 SQNIFGLDVIETPEGDKMPQLIVQKELDREEKDTYVMKVKVEDGGFPQRSSTAILQVSVT 240 SQNIFGLDVIETPEGDKMPQLIVQKELDREEKDTYVMKVKVEDGGFPQRSSTAILQVSVT V. 4 : 181 SQNIFGLDVIETPEGDKMPQLIVQKELDREEKDTYVMKVKVEDGGFPQRSSTAILQVSVT 240 V. 1 : 241 DTNDNHPVFKETEIEVSIPENAPVGTSVTQLHATDADIGENAKIHFSFSNLVSNIARRLF 300 DTNDNHPVFKETEIEVSIPENAPVGTSVTQLHATDADIGENAKIHFSFSNLVSNIARRLF V. 4 : 241 DTNDNHPVFKETEIEVSIPENAPVGTSVTQLHATDADIGENAKIHFSFSNLVSNIARRLF 300 V. 1 : 301 HLNATTGLITIKEPLDREETPNHKLLVLASDGGLMPARAMVLVNVTDVNDNVPSIDIRYI 360 HLNATTGLITIKEPLDREETPNHKLLVLASDGGLMPARAMVLVNVTDVNDNVPSIDIRYI V. 4 : 301 HLNATTGLITIKEPLDREETPNHKLLVLASDGGLMPARAMVLVNVTDVNDNVPSIDIRYI 360 V. 1 : 361 VNPVNDTVVLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLET 420 VNPVNDTWLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLET V. 4 : 361 VNPVNDTWLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLET 420 V. 1 : 421 AAYLDYESTKEYAIKLLAADAGKPPLNQSAMLFIKVKDENDNAPVFTQSFVTVSIPENNS 480 AAYLDYESTKEYAIKLLAADAGKPPLNQSAMLFIKVKDENDNAPVFTQSFVTVSIPENNS V. 4 : 421 AAYLDYESTKEYAIKLLAADAGKPPLNQSAMLFIKVKDENDNAPVFTQSFVTVSIPENNS 480 V. 1 : 481 PGIQLTKVSAMDADSGPNAKINYLLGPDAPPEFSLDCRTGMLTWKKLDREKEDKYLFTI 540 PGIQLTKVSAMDADSGPNAKINYLLGPDAPPEFSLDCRTGMLTWKKLDREKEDKYLFTI V. 4 : 481 PGIQLTKVSAMDADSGPNAKINYLLGPDAPPEFSLDCRTGMLTWKKLDREKEDKYLFTI 540 V. 1 : 541 LAKDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEYNFYVPENLPRHGTVGLITVTDPDYG 600 LAKDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEYNFYVPENLPRHGTVGLITVTDPDYG V. 4 : 541 LAKDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEYNFYVPENLPRHGTVGLITVTDPDYG 600 V. 1 : 601 DNSAVTLSILDENDDFTIDSQTGVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVT 660 DNSAVTLSILDENDDFTIDSQTGVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVT V. 4 : 601 DNSAVTLSILDENDDFTIDSQTGVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVT 660 V. 1 : 661 INWDVNDNKPVFIVPPSNCSYELVLPSTNPGTWFQVIAVDNDTGMNAEVRYSIVGGNT 720 INWDVNDNKPVFIVPPSNCSYELVLPSTNPGTWFQVIAVDNDTGMNAEVRYSIVGGNT V. 4 : 661 INWDVNDNKPVFIVPPSNCSYELVLPSTNPGTWFQVIAVDNDTGMNAEVRYSIVGGNT 720 V. 1 : 721 RDLFAIDQETGNITLMEKCDVTDLGLHRVLVKANDLGQPDSLFSWIVNLFVNESVTNAT 780 RDLFAIDQETGNITLMEKCDVTDLGLHRVLVKANDLGQPDSLFSWIVNLFVNESVTNAT V. 4 : 721 RDLFAIDQETGNITLMEKCDVTDLGLHRVLVKANDLGQPDSLFSWIVNLFVNESVTNAT 780 V. 1 : 781 LINELVRKSTEAPVTPNTEIADVSSPTSDYVKILVAAVAGTITWWIFITAWRCRQAP 840 LINELVRKSTEAPVTPNTEIADVSSPTSDYVKILVAAVAGTITWWIFITAWRCRQAP V. 4 : 781 LINELVRKSTEAPVTPNTEIADVSSPTSDYVKILVAAVAGTITWWIFITAWRCRQAP 840 V. 1 : 841 HLKAAQKNKQNSEWATPNPENRQMIMMKKKKKKKKHSPKNLLLNFVTIEETKADDVDSDG 900 HLKAAQKNKQNSEWATPNPENRQMIMMKKKKKKKKHSPKNLLLNFVTIEETKADDVDSDG V. 4 : 841 HLKAAQKNKQNSEWATPNPENRQMIMMKKKKKKKKHSPKNLLLNFVTIEETKADDVDSDG 900 V. 1 : 901 NRVTLDLPIDLEEQTMGKYNWVTTPTTFKPDSPDLARHYKSASPQPAFQIQPETPLNSKH 960 NRVTLDLPIDLEEQTMGKYNWVTTPTTFKPDSPDLARHYKSASPQPAFQIQPETPLNSKH V. 4 : 901 NRVTLDLPIDLEEQTMGKYNWVTTPTTFKPDSPDLARHYKSASPQPAFQIQPETPLNSKH 960 V. 1 : 961 HIIQELPLDNTFVACDSISKCSSSSSDPYSVSDCGYPVTTFEVPVSVHTRP 1011 HIIQELPLDNTFVACDSISKCSSSSSDPYSVSDCGYPVTTFEVPVSVHTRP V. 4 : 961 HIIQELPLDNTFVACDSISKCSSSSSDPYSVSDCGYPVTTFEVPVSVHTRP 1011 Table LII (d). Nucleotide sequence of transcript variant 109P1D4 v. 5 (SEQ ID NO : 255) ctggtggtcc agtacctcca aagatatgga atacactcct gaaatatcct gaaaactttt 60 ttttttcaga atcctttaat aagcagttat gtcaatctga aagttgctta cttgtacttt 120 atattaatag ctattcttgt ttttcttatc caaagaaaaa tcctctaatc cccttttcac 180 atgatagttg ttaccatgtt taggcattag tcacatcaac ccctctcctc tcccaaactt 240 ctcttcttca aatcaaactt tattagtccc tcctttataa tgattccttg cctcgtttta 300 tccagatcaa ttttttttca ctttgatgcc cagagctgaa gaaatggact actgtataaa 360 ttattcattg ccaagagaat aattgcattt taaacccata ttataacaaa gaataatgat 420 tatattttgt gatttgtaac aaataccctt tattttccct taactattga attaaatatt 480 ttaattattt gtattctctt taactatctt ggtatattaa agtattatct tttatatatt 540 tatcaatggt ggacactttt ataggtactc tgtgtcattt ttgatactgt aggtatctta 600 tttcatttat ctttattctt aatgtacgaa ttcataatat ttgattcaga acaaatttat 660 cactaattaa cagagtgtca attatgctaa catctcattt actgatttta atttaaaaca 720 gtttttgtta acatgcatgt ttagggttgg cttcttaata atttcttctt cctcttctct 780 ctctcctctt cttttggtca gtgttgtgcg ggttaataca acaaactgta acaagtgtac 840 ctggtatgga cttgttgtcc gggacgtaca ttttcgcggt cctgctagca tgcgtggtgt 900 tccactctgg cgcccaggag aaaaactaca ccatccgaga agaaatgcca gaaaacgtcc 960 tgataggcga cttgttgaaa gaccttaact tgtcgctgat tccaaacaag tccttgacaa 1020 ctgctatgca gttcaagcta gtgtacaaga ccggagatgt gccactgatt cgaattgaag 1080 aggatactgg tgagatcttc actactggcg ctcgcattga tcgtgagaaa ttatgtgctg 1140 gtatcccaag ggatgagcat tgcttttatg aagtggaggt tgccattttg ccggatgaaa 1200 tatttagact ggttaagata cgttttctga tagaagatat aaatgataat gcaccattgt 1260 tcccagcaac agttatcaac atatcaattc cagagaactc ggctataaac tctaaatata 1320 ctctcccagc ggctgttgat cctgacgtag gaataaacgg agttcaaaac tacgaactaa 1380 ttaagagtca aaacattttt ggcctcgatg tcattgaaac accagaagga gacaagatgc 1440 cacaactgat tgttcaaaag gagttagata gggaagagaa ggatacctac gtgatgaaag 1500 taaaggttga agatggtggc tttcctcaaa gatccagtac tgctattttg caagtgagtg 1560 ttactgatac aaatgacaac cacccagtct ttaaggagac agagattgaa gtcagtatac 1620 cagaaaatgc tcctgtaggc acttcagtga cacagctcca tgccacagat gctgacatag 1680 gtgaaaatgc caagatccac ttctctttca gcaatctagt ctccaacatt gccaggagat 1740 tatttcacct caatgccacc actggactta tcacaatcaa agaaccactg gatagggaag 1800 aaacaccaaa ccacaagtta ctggttttgg caagtgatgg tggattgatg ccagcaagag 1860 caatggtgct ggtaaatgtt acagatgtca atgataatgt cccatccatt gacataagat 1920 acatcgtcaa tcctgtcaat gacacagttg ttctttcaga aaatattcca ctcaacacca 1980 aaattgctct cataactgtg acggataagg atgcggacca taatggcagg gtgacatgct 2040 tcacagatca tgaaatccct ttcagattaa ggccagtatt cagtaatcag ttcctcctgg 2100 agactgcagc atatcttgac tatgagtcca caaaagaata tgccattaaa ttactggctg 2160 cagatgctgg caaacctcct ttgaatcagt cagcaatgct cttcatcaaa gtgaaagatg 2220 aaaatgacaa tgctccagtt ttcacccagt ctttcgtaac tgtttctatt cctgagaata 2280 actctcctgg catccagttg acgaaagtaa gtgcaatgga tgcagacagt gggcctaatg 2340 ctaagatcaa ttacctgcta ggccctgatg ctccacctga attcagcctg gattgtcgta 2400 caggcatgct gactgtagtg aagaaactag atagagaaaa agaggataaa tatttattca 2460 caattctggc aaaagataac ggggtaccac ccttaaccag caatgtcaca gtctttgtaa 2520 gcattattga tcagaatgac aatagcccag ttttcactca caatgaatac aacttctatg 2580 tcccagaaaa ccttccaagg catggtacag taggactaat cactgtaact gatcctgatt 2640 atggagacaa ttctgcagtt acgctctcca ttttagatga gaatgatgac ttcaccattg 2700 attcacaaac tggtgtcatc cgaccaaata tttcatttga tagagaaaaa caagaatctt 2760 acactttcta tgtaaaggct gaggatggtg gtagagtatc acgttcttca agtgccaaag 2820 taaccataaa tgtggttgat gtcaatgaca acaaaccagt tttcattgtc cctccttcca 2880 actgttctta tgaattggtt ctaccgtcca ctaatccagg cacagtggtc tttcaggtaa 2940 ttgctgttga caatgacact ggcatgaatg cagaggttcg ttacagcatt gtaggaggaa 3000 acacaagaga tctgtttgca atcgaccaag aaacaggcaa cataacattg atggagaaat 3060 gtgatgttac agaccttggt ttacacagag tgttggtcaa agctaatgac ttaggacagc 3120 ctgattctct cttcagtgtt gtaattgtca atctgttcgt gaatgagtcg gtgaccaatg 3180 ctacactgat taatgaactg gtgcgcaaaa gcactgaagc accagtgacc ccaaatactg 3240 agatagctga tgtatcctca ccaactagtg actatgtcaa gatcctggtt gcagctgttg 3300 ctggcaccat aactgtcgtt gtagttattt tcatcactgc tgtagtaaga tgtcgccagg 3360 caccacacct taaggctgct cagaaaaaca agcagaattc tgaatgggct accccaaacc 3420 cagaaaacag gcagatgata atgatgaaga aaaagaaaaa gaagaagaag cattccccta 3480 agaacttgct gcttaatttt gtcactattg aagaaactaa ggcagatgat gttgacagtg 3540 atggaaacag agtcacacta gaccttccta ttgatctaga agagcaaaca atgggaaagt 3600 acaattgggt aactacacct actactttca agcccgacag ccctgatttg gcccgacact 3660 acaaatctgc ctctccacag cctgccttcc aaattcagcc tgaaactccc ctgaattcga 3720 agcaccacat catccaagaa ctgcctctcg ataacacctt tgtggcctgt gactctatct 3780 ccaagtgttc ctcaagcagt tcagatccct acagcgtttc tgactgtggc tatccagtga 3840 cgaccttcga ggtacctgtg tccgtacaca ccagaccgtc ccagcggcgt gtcacatttc 3900 acctgccaga aggctctcag gaaagcagca gtgatggtgg actgggagac catgatgcag 3960 gcagccttac cagcacatct catggcctgc cccttggcta tcctcaggag gagtactttg 4020 atcgtgctac acccagcaat cgcactgaag gggatggcaa ctccgatcct gaatctactt 4080 tcatacctgg actaaagaaa gctgcagaaa taactgttca accaactgtg gaagaggcct 4140 ctgacaactg cactcaagaa tgtctcatct atggccattc tgatgcctgc tggatgccgg 4200 catctctgga tcattccagc tcttcgcaag cacaggcctc tgctctatgc cacagcccac 4260 cactgtcaca ggcctctact cagcaccaca gcccacgagt gacacagacc attgctctct 4320 gccacagccc tccagtgaca cagaccatcg cattgtgcca cagcccacca ccgatacagg 4380 tgtctgctct ccaccacagt cctcctctag tgcaggctac tgcacttcac cacagcccac 4440 catcagcaca ggcctcagcc ctctgctaca gccctccttt agcacaggct gctgcaatca 4500 gccacagctc tcctctgcca caggttattg ccctccatcg tagtcaggcc caatcatcag 4560 tcagtttgca gcaaggttgg gtgcaaggtg ctgatgggct atgctctgtt gatcagggag 4620 tgcaaggtag tgcaacatct cagttttaca ccatgtctga aagacttcat cccagtgatg 4680 attcaattaa agtcattcct ttgacaacct tcactccacg ccaacaggcc agaccgtcca 4740 gaggtgattc ccccattatg gaagaacatc ccttgtaaag ctaaaatagt tacttcaaat 4800 tttcagaaaa gatgtatata gtcaaaattt aagatacaat tccaatgagt attctgatta 4860 tcagatttgt aaataactat gtaaatagaa acagatacca gaataaatct acagctagac 4920 ccttagtcaa tagttaacca aaaaattgca atttgtttaa ttcagaatgt gtatttaaaa 4980 agaaaaggaa tttaacaatt tgcatcccct tgtacagtaa ggcttatcat gacagagcgc 5040 actatttctg atgtacagta ttttttgttg tttttatcat catgtgcaat attactgatt 5100 tgtttccatg ctgattgtgt ggaaccagta tgtagcaaat ggaaagccta gaaatatctt 5160 attttctaag tttaccttta gtttacctaa acttttgttc agataacgtt aaaaggtata 5220 cgtactctag cctttttttg ggctttcttt ttgatttttg tttgttgttt tcagtttttt 5280 tgttgttgtt agtgagtctc ccttcaaaat acgcagtagg tagtgtaaat actgcttgtt 5340 tgtgtctctc tgctgtcatg ttttctacct tattccaata ctatattgtt gataaaattt 5400 gtatatacat tttcaataaa gaatatgtat aaactgtaca gatctagatc tacaacctat 5460 ttctctactc tttagtagag ttcgagacac agaagtgcaa taactgccct aattaagcaa 5520 ctatttgtta aaaagggcct ctttttactt taatagttta gtgtaaagta catcagaaat 5580 aaagctgtat ctgccatttt aagcctgtag tccattatta cttgggtctt tacttctggg 5640 aatttgtatg taacagccta gaaaattaaa aggaggtgga tgcatccaaa gcacgagtca 5700 cttaaaatat cgacggtaaa ctactatttt gtagagaaac tcaggaagat ttaaatgttg 5760 atttgacagc tcaataggct gttaccaaag ggtgttcagt aaaaataaca aatacatgta 5820 actgtagata aaaccatata ctaaatctat aagactaagg gatttttgtt attctagctc 5880 aacttactga agaaaaccac taataacaac aagaatatca ggaaggaact tttcaagaaa 5940 tgtaattata aatctacatc aaacagaatt ttaaggaaaa atgcagaggg agaaataagg 6000 cacatgactg cttcttgcag tcaacaagaa ataccaataa cacacacaga acaaaaacca 6060 tcaaaatctc atatatgaaa taaaatatat tcttctaagc aaagaaacag tactattcat 6120 agaaaacatt agttttcttc tgttgtctgt tatttccttc ttgtatcctc ttaactggcc 6180 attatcttgt atgtgcacat tttataaatg tacagaaaca tcaccaactt aattttcttc 6240 catagcaaaa ctgagaaaat accttgtttc agtataacac taaaccaaga gacaattgat 6300 gtttaatggg ggcggttggg gtgggggggg gagtcaatat ctcctattga ttaacttaga 6360 catagatttt gtaatgtata acttgatatt taatttatga ttaaactgtg tgtaaatttt 6420 gtaacataaa ctgtggtaat tgcataattt cattggtgag gatttccact gaatattgag 6480 aaagtttctt ttcatgtgcc cagcaggtta agtagcgttt tcagaatata cattattccc 6540 atccattgta aagttcctta agtcatattt gactgggcgt gcagaataac ttcttaactt 6600 ttaactatca gagtttgatt aataaaatta attaatgttt tttctccttc gtgttgttaa 6660 tgttccaagg gatttggagc atactggttt tccaggtgca tgtgaatccc gaaggactga 6720 tgatatttga atgtttatta aattattatc atacaaatgt gttgatattg tggctattgt 6780 tgatgttgaa aattttaaac ttggggaaga ttaagaaaag aaccaatagt gacaaaaatc 6840 agtgcttcca gtagatttta gaacattctt tgcctcaaaa aacctgcaaa gatgatgtga 6900 gattttttct tgtgttttaa ttattttcac attttctctc tgcaaaactt tagttttctg 6960 atgatctaca cacacacaca cacacacacg tgcacacaca cacacattta aatgatataa 7020 aaagaagagg ttgaaagatt attaaataac ttatcaggca tctcaatggt tactatctat 7080 gttagtgaaa atcaaatagg actcaaagtt ggatatttgg gatttttctt ctgacagtat 7140 aatttattga gttactaggg aggttcttaa atcctcatat ctggaaactt gtgacgtttt 7200 gacacctttc ctatagatga tataggaatg aaccaatacg cttttattac cctttctaac 7260 tctgatttta taatcagact tagattgtgt ttagaatatt aaatgactgg gcaccctctt 7320 cttggttttt accagagagg ctttgaatgg aagcaggctg agagtagcca aagaggcaag 7380 gggtattagc ccagttattc tcccctatgc cttccttctc tttctaagcg tccactaggt 7440 ctggccttgg aaacctgtta cttctagggc ttcagatctg atgatatctt tttcatcaca 7500 ttacaagtta tttctctgac tgaatagaca gtggtatagg ttgacacagc acacaagtgg 7560 ctattgtgat gtatgatgta tgtagtccta caactgcaaa acgtcttact gaaccaacaa 7620 tcaaaaaatg gttctgtttt aaaaaggatt ttgtttgatt tgaaattaaa acttcaagct 7680 gaatgactta tatgagaata atacgttcaa tcaaagtagt tattctattt tgtgtccata 7740 ttccattaga ttgtgattat taattttcta gctatggtat tactatatca cacttgtgag 7800 tatgtattca aatactaagt atcttatatg ctacgtgcat acacattctt ttcttaaact 7860 ttacctgtgt tttaactaat attgtgtcag tgtattaaaa attagctttt acatatgata 7920 tctacaatgt aataaattta gagagtaatt ttgtgtattc ttatttactt aacattttac 7980 ttttaattat gtaaatttgg ttagaaaata ataataaatg gttagtgcta ttgtgtaatg 8040 gtagcagtta caaagagcct ctgccttccc aaactaatat ttatcacaca tggtcattaa 8100 atgggaaaaa aatagactaa acaaatcaca aattgttcag ttcttaaaat gtaattatgt 8160 cacacacaca aaaaatcctt ttcaatcctg agaaaattaa aggcgtttta ctcacatggc 8220 tatttcaaca ttagtttttt ttgtttgttt ctttttcatg gtattactga aggtgtgtat 8280 actccctaat acacatttat gaaaatctac ttgtttaggc ttttatttat actcttctga 8340 tttatatttt ttattataat tattatttct tatctttctt cttttatatt ttttggaaac 8400 caaatttata gttagtttag gtaaactttt tattatgacc attagaaact attttgaatg 8460 cttccaactg gctcaattgg ccgggaaaac atgggagcaa gagaagctga aatatatttc 8520 tgcaagaacc tttctatatt atgtgccaat taccacacca gatcaatttt atgcagaggc 8580 cttaaaatat tctttcacag tagctttctt acactaaccg tcatgtgctt ttagtaaata 8640 tgatttttaa aagcagttca agttgacaac agcagaaaca gtaacaaaaa aatctgctca 8700 gaaaaatgta tgtgcacaaa taaaaaaaat taatggcaat tgtttagtga ttgtaagtga 8760 tactttttaa agagtaaact gtgtgaaatt tatactatcc ctgcttaaaa tattaagatt 8820 tttatgaaat atgtatttat gtttgtattg tgggaagatt cctcctctgt gatatcatac 8880 agcatctgaa agtgaacagt atcccaaagc agttccaacc atgctttgga agtaagaagg 8940 ttgactattg tatggccaag gatggcagta tgtaatccag aagcaaactt gtattaattg 9000 ttctatttca ggttctgtat tgcatgtttt cttattaata tatattaata aaagttatga 9060 gaaat 9065 Table Lull (d). Nucleotide sequence alignment of 109P1 D4 v. 1 (SEQ ID NO : 256) and 109P1D4 v. 5 (SEQ ID NO : 257) Score = 7456 bits (3878), Expect = O. Oldentities = 3878/3878 (100%) Strand = Plus/Plus V. 1 : 1 ctggtggtccagtacctccaaagatatggaatacactcctgaaatatcctgaaaactttt 60 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 5 1 ctggtggtccagtacctccaaagatatggaatacactcctgaaatatcctgaaaactttt 60 V. 1 : 61 ttttttcagaatcctttaataagcagttatgtcaatctgaaagttgcttacttgtacttt 120 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 5 : 61 ttttttcagaatcctttaataagcagttatgtcaatctgaaagttgcttacttgtacttt 120 V. 1 : 121 atattaatagctattcttgtttttcttatccaaagaaaaatcctctaatccccttttcac 180 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 5 : 121 atattaatagctattcttgtttttcttatccaaagaaaaatcctctaatccccttttcac 180 V. 1 : 181 atgatagttgttaccatgtttaggcattagtcacatcaacccctctcctctcccaaactt 240 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII1111111111111 V. 5 : 181 atgatagttgttaccatgtttaggcattagtcacatcaacccctctcctctcccaaactt 240 V. 1 : 241 ctcttcttcaaatcaaactttattagtccctcctttataatgattccttgcctcgtttta 300 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 5 : 241 ctcttcttcaaatcaaactttattagtccctcctttataatgattccttgcctcgtttta 300 V. 1 : 301 tccagatcaattttttttcactttgatgcccagagctgaagaaatggactactgtataaa 360 IIIlllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 5 : 301 tccagatcaattttttttcactttgatgcccagagctgaagaaatggactactgtataaa 360 V. 1 361 ttattcattgccaagagaataattgcattttaaacccatattataacaaagaataatgat 420 Illlllllllllllllllllllllllllllllllllllllllllllllllllllll V. 5 : 361 ttattcattgccaagagaataattgcattttaaacccatattataacaaagaataatgat 420 V. 1 : 421 tatattttgtgatttgtaacaaataccctttattttcccttaactattgaattaaatatt 480 Illllllllllllllillllllllllllllllllllllllllilllllllllllllllll V. 5 : 421 tatattttgtgatttgtaacaaataccctttattttcccttaactattgaattaaatatt 480 V.'l 481 ttaattatttgtattctctttaactatcttggtatattaaagtattatcttttatatatt 540 Illlllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 5 : 481 ttaattatttgtattctctttaactatcttggtatattaaagtattatcttttatatatt 540 V. 1 : 541 tatcaatggtggacacttttataggtactctgtgtcatttttgatactgtaggtatctta 600 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 5 : 541 tatcaatggtggacacttttataggtactctgtgtcatttttgatactgtaggtatctta 600 V. 1 : 601 tttcatttatctttattcttaatgtacgaattcataatatttgattcagaacaaatttat 660 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 5 601 tttcatttatctttattcttaatgtacgaattcataatatttgattcagaacaaatttat 660 V. 1 661 cactaattaacagagtgtcaattatgctaacatctcatttactgattttaatttaaaaca 720 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 5 : 661 cactaattaacagagtgtcaattatgctaacatctcatttactgattttaatttaaaaca 720 V. 1 : 721 gtttttgttaacatgcatgtttagggttggcttcttaataatttcttcttcctcttctct 780 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 5 : 721 gtttttgttaacatgcatgtttagggttggcttcttaataatttcttcttcctcttctct 780 V. 1 : 781 ctctcctcttcttttggtcagtgttgtgcgggttaatacaacaaactgtaacaagtgtac 840 Illllllllllllllllllllllllllllllllllllllllllllllllllll lllllll V. 5 781 ctctcctcttcttttggtcagtgttgtgcgggttaatacaacaaactgtaacaagtgtac 840 V. 1 841 ctggtatggacttgttgtccgggacgtacattttcgcggtcctgctagcatgcgtggtgt 900 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 5 : 841 ctggtatggacttgttgtccgggacgtacattttcgcggtcctgctagcatgcgtggtgt 900 V. 1 901 tccactctggcgcccaggagaaaaactacaccatccgagaagaaatgccagaaaacgtcc 960 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 5 : 901 tccactctggcgcccaggagaaaaactacaccatccgagaagaaatgccagaaaacgtcc 960 V. 1 : 961 tgataggcgacttgttgaaagaccttaacttgtcgctgattccaaacaagtccttgacaa 1020 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 5 : 961 tgataggcgacttgttgaaagaccttaacttgtcgctgattccaaacaagtccttgacaa 1020 V. 1 : 1021 ctgctatgcagttcaagctagtgtacaagaccggagatgtgccactgattcgaattgaag 1080 Illlllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 5 : 1021 ctgctatgcagttcaagctagtgtacaagaccggagatgtgccactgattcgaattgaag 1080 V. 1 : 1081 aggatactggtgagatcttcactactggcgctcgcattgatcgtgagaaattatgtgctg 1140 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIillllllll V. 5 : 1081 aggatactggtgagatcttcactactggcgctcgcattgatcgtgagaaattatgtgctg 1140 V. 1 : 1141 gtatcccaagggatgagcattgcttttatgaagtggaggttgccattttgccggatgaaa 1200 llllllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 5 : 1141 gtatcccaagggatgagcattgcttttatgaagtggaggttgccattttgccggatgaaa 1200 V. 1 : 1201 tatttagactggttaagatacgttttctgatagaagatataaatgataatgcaccattgt 1260 IIIlllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 5 : 1201 tatttagactggttaagatacgttttctgatagaagatataaatgataatgcaccattgt 1260 V. 1 : 1261 tcccagcaacagttatcaacatatcaattccagagaactcggctataaactctaaatata 1320 Illlllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 5 : 1261 tcccagcaacagttatcaacatatcaattccagagaactcggctataaactctaaatata 1320 V. 1 : 1321 ctctcccagcggctgttgatcctgacgtaggaataaacggagttcaaaactacgaactaa 1380 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 5 : 1321 ctctcccagcggctgttgatcctgacgtaggaataaacggagttcaaaactacgaactaa 1380 V. 1 : 1381 ttaagagtcaaaacatttttggcctcgatgtcattgaaacaccagaaggagacaagatgc 1440 llllllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 5 : 1381 ttaagagtcaaaacatttttggcctcgatgtcattgaaacaccagaaggagacaagatgc 1440 V. 1 : 1441 cacaactgattgttcaaaaggagttagatagggaagagaaggatacctacgtgatgaaag 1500 IIIlllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 5 : 1441 cacaactgattgttcaaaaggagttagatagggaagagaaggatacctacgtgatgaaag 1500 V. 1 : 1501 taaaggttgaagatggtggctttcctcaaagatccagtactgctattttgcaagtgagtg 1560 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 5 : 1501 taaaggttgaagatggtggctttcctcaaagatccagtactgctattttgcaagtgagtg 1560 V. 1 : 1561 ttactgatacaaatgacaaccacccagtctttaaggagacagagattgaagtcagtatac 1620 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 5 : 1561 ttactgatacaaatgacaaccacccagtctttaaggagacagagattgaagtcagtatac 1620 V. 1 : 1621 cagaaaatgctcctgtaggcacttcagtgacacagctccatgccacagatgctgacatag 1680 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 5 : 1621 cagaaaatgctcctgtaggcacttcagtgacacagctccatgccacagatgctgacatag 1680 V. 1 : 1681 gtgaaaatgccaagatccacttctctttcagcaatctagtctccaacattgccaggagat 1740 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 5 : 1681 gtgaaaatgccaagatccacttctctttcagcaatctagtctccaacattgccaggagat 1740 V. 1 : 1741 tatttcacctcaatgccaccactggacttatcacaatcaaagaaccactggatagggaag 1800 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII, IIIIIIIIII V. 5 : 1741 tatttcacctcaatgccaccactggacttatcacaatcaaagaaccactggatagggaag 1800 V. 1 : 1801 aaacaccaaaccacaagttactggttttggcaagtgatggtggattgatgccagcaagag 1860 Illlllllllllllllllllllllllllllllllllllllllllllllllllilllllll V. 5 : 1801 aaacaccaaaccacaagttactggttttggcaagtgatggtggattgatgccagcaagag 1860 V. 1 : 1861 caatggtgctggtaaatgttacagatgtcaatgataatgtcccatccattgacataagat 1920 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 5 1861 caatggtgctggtaaatgttacagatgtcaatgataatgtcccatccattgacataagat 1920 V. 1 : 1921 acatcgtcaatcctgtcaatgacacagttgttctttcagaaaatattccactcaacacca 1980 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 5 : 1921 acatcgtcaatcctgtcaatgacacagttgttctttcagaaaatattccactcaacacca 1980 V. 1 : 1981 aaattgctctcataactgtgacggataaggatgcggaccataatggcagggtgacatgct 2040 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 5 : 1981 aaattgctctcataactgtgacggataaggatgcggaccataatggcagggtgacatgct 2040 V. 1 : 2041 tcacagatcatgaaatccctttcagattaaggccagtattcagtaatcagttcctcctgg 2100 1111111111111|1111111111111111111111111111111111111111111111 V. 5 : 2041 tcacagatcatgaaatccctttcagattaaggccagtattcagtaatcagttcctcctgg 2100 V. 1 : 2101 agactgcagcatatcttgactatgagtccacaaaagaatatgccattaaattactggctg 2160 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 5 : 2101 agactgcagcatatcttgactatgagtccacaaaagaatatgccattaaattactggctg 2160 V. 1 : 2161 cagatgctggcaaacctcctttgaatcagtcagcaatgctcttcatcaaagtgaaagatg 2220 Illlllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 5 : 2161 cagatgctggcaaacctcctttgaatcagtcagcaatgctcttcatcaaagtgaaagatg 2220 V. 1 : 2221 aaaatgacaatgctccagttttcacccagtctttcgtaactgtttctattcctgagaata 2280 IIIlllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 5 : 2221 aaaatgacaatgctccagttttcacccagtctttcgtaactgtttctattcctgagaata 2280 V. 1 : 2281 actctcctggcatccagttgacgaaagtaagtgcaatggatgcagacagtgggcctaatg 2340 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 5 : 2281 actctcctggcatccagttgacgaaagtaagtgcaatggatgcagacagtgggcctaatg 2340 V. 1 : 2341 ctaagatcaattacctgctaggccctgatgctccacctgaattcagcctggattgtcgta 2400 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 5 : 2341 ctaagatcaattacctgctaggccctgatgctccacctgaattcagcctggattgtcgta 2400 V. 1 : 2401 caggcatgctgactgtagtgaagaaactagatagagaaaaagaggataaatatttattca 2460 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 5 : 2401 caggcatgctgactgtagtgaagaaactagatagagaaaaagaggataaatatttattca 2460 V. 1 : 2461 caattctggcaaaagataacggggtaccacccttaaccagcaatgtcacagtctttgtaa 2520 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 5 : 2461 caattctggcaaaagataacggggtaccacccttaaccagcaatgtcacagtctttgtaa 2520 V. 1 : 2521 gcattattgatcagaatgacaatagcccagttttcactcacaatgaatacaacttctatg 2580 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 5 : 2521 gcattattgatcagaatgacaatagcccagttttcactcacaatgaatacaacttctatg 2580 V. 1 : 2581 tcccagaaaaccttccaaggcatggtacagtaggactaatcactgtaactgatcctgatt 2640 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 5 : 2581 tcccagaaaaccttccaaggcatggtacagtaggactaatcactgtaactgatcctgatt 2640 V. 1 : 2641 atggagacaattctgcagttacgctctccattttagatgagaatgatgacttcaccattg 2700 Illlllllllllllllllllllllllllllllllllllllllllllllllllilllllll V. 5 : 2641 atggagacaattctgcagttacgctctccattttagatgagaatgatgacttcaccattg 2700 V. 1 : 2701 attcacaaactggtgtcatccgaccaaatatttcatttgatagagaaaaacaagaatctt 2760 Illllllllllllllllllllllllllilllllllllllllllllillllllllllllll V. 5 : 2701 attcacaaactggtgtcatccgaccaaatatttcatttgatagagaaaaacaagaatctt 2760 V. 1 : 2761 acactttctatgtaaaggctgaggatggtggtagagtatcacgttcttcaagtgccaaag 2820 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 5 : 2761 acactttctatgtaaaggctgaggatggtggtagagtatcacgttcttcaagtgccaaag 2820 V. 1 : 2821 taaccataaatgtggttgatgtcaatgacaacaaaccagttttcattgtccctccttcca 2880 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 5 : 2821 taaccataaatgtggttgatgtcaatgacaacaaaccagttttcattgtccctccttcca 2880 V. 1 : 2881 actgttcttatgaattggttctaccgtccactaatccaggcacagtggtctttcaggtaa 2940 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 5 2881 actgttcttatgaattggttctaccgtccactaatccaggcacagtggtctttcaggtaa 2940 V. 1 : 2941 ttgctgttgacaatgacactggcatgaatgcagaggttcgttacagcattgtaggaggaa 3000 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 5 : 2941 ttgctgttgacaatgacactggcatgaatgcagaggttcgttacagcattgtaggaggaa 3000 V. 1 : 3001 acacaagagatctgtttgcaatcgaccaagaaacaggcaacataacattgatggagaaat 3060 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 5 : 3001 acacaagagatctgtttgcaatcgaccaagaaacaggcaacataacattgatggagaaat 3060 V. 1 : 3061 gtgatgttacagaccttggtttacacagagtgttggtcaaagctaatgacttaggacagc 3120 111111111111111111111|11111111111111111111111111111111111|11 V. 5 : 3061 gtgatgttacagaccttggtttacacagagtgttggtcaaagctaatgacttaggacagc 3120 V. 1 : 3121 ctgattctctcttcagtgttgtaattgtcaatctgttcgtgaatgagtcggtgaccaatg 3180 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 5 : 3121 ctgattctctcttcagtgttgtaattgtcaatctgttcgtgaatgagtcggtgaccaatg 3180 V. 1 : 3181 ctacactgattaatgaactggtgcgcaaaagcactgaagcaccagtgaccccaaatactg 3240 Illlllllilllllllllllllllllllllllllllllllllllllllllllllllllll V. 5 : 3181 ctacactgattaatgaactggtgcgcaaaagcactgaagcaccagtgaccccaaatactg 3240 V. 1 : 3241 agatagctgatgtatcctcaccaactagtgactatgtcaagatcctggttgcagctgttg 3300 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 5 : 3241 agatagctgatgtatcctcaccaactagtgactatgtcaagatcctggttgcagctgttg 3300 V. 1 : 3301 ctggcaccataactgtcgttgtagttattttcatcactgctgtagtaagatgtcgccagg 3360 Illlllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 5 : 3301 ctggcaccataactgtcgttgtagttattttcatcactgctgtagtaagatgtcgccagg 3360 V. 1 : 3361 caccacaccttaaggctgctcagaaaaacaagcagaattctgaatgggctaccccaaacc 3420 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 5 : 3361 caccacaccttaaggctgctcagaaaaacaagcagaattctgaatgggctaccccaaacc 3420 V. 1 : 3421 cagaaaacaggcagatgataatgatgaagaaaaagaaaaagaagaagaagcattccccta 3480 Illlllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 5 : 3421 cagaaaacaggcagatgataatgatgaagaaaaagaaaaagaagaagaagcattccccta 3480 V. 1 : 3481 agaacttgctgcttaattttgtcactattgaagaaactaaggcagatgatgttgacagtg 3540 Illllllllllllllllllllllllllillllllllllllllllllllllllllllllll V. 5 : 3481 agaacttgctgcttaattttgtcactattgaagaaactaaggcagatgatgttgacagtg 3540 V. 1 : 3541 atggaaacagagtcacactagaccttcctattgatctagaagagcaaacaatgggaaagt 3600 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 5 : 3541 atggaaacagagtcacactagaccttcctattgatctagaagagcaaacaatgggaaagt 3600 V. 1 : 3601 acaattgggtaactacacctactactttcaagcccgacagccctgatttggcccgacact 3660 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 5 : 3601 acaattgggtaactacacctactactttcaagcccgacagccctgatttggcccgacact 3660 V. 1 : 3661 acaaatctgcctctccacagcctgccttccaaattcagcctgaaactcccctgaattcga 3720 llllllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 5 : 3661 acaaatctgcctctccacagcctgccttccaaattcagcctgaaactcccctgaattcga 3720 V. 1 : 3721 agcaccacatcatccaagaactgcctctcgataacacctttgtggcctgtgactctatct 3780 Illllllllllllillllllllllllllllllllllllllllllllllllllllllllll V. 5 : 3721 agcaccacatcatccaagaactgcctctcgataacacctttgtggcctgtgactctatct 3780 V. 1 : 3781 ccaagtgttcctcaagcagttcagatccctacagcgtttctgactgtggctatccagtga 3840 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 5 : 3781 ccaagtgttcctcaagcagttcagatccctacagcgtttctgactgtggctatccagtga 3840 V. 1 : 3841 cgaccttcgaggtacctgtgtccgtacacaccagaccg 3878 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 5 : 3841 cgaccttcgaggtacctgtgtccgtacacaccagaccg 3878 Table LIV (d). Peptide sequences of protein coded by 109P1D4 v. 5 (SEQ ID NO : 258) MDLLSGTYIF AVLLACVVFH SGAQEKNYTI REEMPENVLI GDLLKDLNLS LIPNKSLTTA 60 MQFKLVYKTG DVPLIRIEED TGEIFTTGAR IDREKLCAGI PRDEHCFYEV EVAILPDEIF 120 RLVKIRFLIE DINDNAPLFP ATVINISIPE NSAINSKYTL PAAVDPDVGI NGVQNYELIK 180 SQNIFGLDVI ETPEGDKMPQ LIVQKELDRE EKDTYVMKVK VEDGGFPQRS STAILQVSVT 240 DTNDNHPVFK ETEIEVSIPE NAPVGTSVTQ LHATDADIGE NAKIHFSFSN LVSNIARRLF 300 HLNATTGLIT IKEPLDREET PNHKLLVLAS DGGLMPARAM VLVNVTDVND NVPSIDIRYI 360 VNPVNDTVVL SENIPLNTKI ALITVTDKDA DHNGRVTCFT DHEIPFRLRP VFSNQFLLET 420 AAYLDYESTK EYAIKLLAAD AGKPPLNQSA MLFIKVKDEN DNAPVFTQSF VTVSIPENNS 480 PGIQLTKVSA MDADSGPNAK INYLLGPDAP PEFSLDCRTG MLTVVKKLDR EKEDKYLFTI 540 LAKDNGVPPL TSNVTVFVSI IDQNDNSPVF THNEYNFYVP ENLPRHGTVG LITVTDPDYG 600 DNSAVTLSIL DENDDFTIDS QTGVIRPNIS FDREKQESYT FYVKAEDGGR VSRSSSAKVT 660 INVVDVNDNK PVFIVPPSNC SYELVLPSTN PGTVVFQVIA VDNDTGMNAE VRYSIVGGNT 720 RDLFAIDQET GNITLMEKCD VTDLGLHRVL VKANDLGQPD SLFSVVIVNL FVNESVTNAT 780 LINELVRKST EAPVTPNTEI ADVSSPTSDY VKILVAAVAG TITVVVVIFI TAVVRCRQAP 840 HLKAAQKNKQ NSEWATPNPE NRQMIMMKKK KKKKKHSPKN LLLNFVTIEE TKADDVDSDG 900 NRVTLDLPID LEEQTMGKYN WVTTPTTFKP DSPDLARHYK SASPQPAFQI QPETPLNSKH 960 HIIQELPLDN TFVACDSISK CSSSSSDPYS VSDCGYPVTT FEVPVSVHTR PSQRRVTFHL 1020 PEGSQESSSD GGLGDHDAGS LTSTSHGLPL GYPQEEYFDR ATPSNRTEGD GNSDPESTFI 1080 PGLKKAAEIT VQPTVEEASD NCTQECLIYG HSDACWMPAS LDHSSSSQAQ ASALCHSPPL 1140 SQASTQHHSP RVTQTIALCH SPPVTQTIAL CHSPPPIQVS ALHHSPPLVQ ATALHHSPPS 1200 AQASALCYSP PLAQAAAISH SSPLPQVIAL HRSQAQSSVS LQQGWVQGAD GLCSVDQGVQ 1260 GSATSQFYTM SERLHPSDDS IKVIPLTTFT PRQQARPSRG DSPIMEEHPL 1310 Table LV (d). Amino acid sequence alignment of 109P1D4 v.1 (SEQ ID NO : 259) and 109P1D4 v.5 (SEQ ID NO : 260) Score = 2005 bits (5195), Expect = O. Oldentities = 1011/1011 (100%), Positives = 1011/1011 (100%) V. 1 : 1 MDLLSGTYIFAVLLACWFHSGAQEKNYTIREEMPENVLIGDLLKDLNLSLIPNKSLTTA 60 MDLLSGTYIFAVLLACWFHSGAQEKNYTIREEMPENVLIGDLLKDLNLSLIPNKSLTTA V. 5 : 1 MDLLSGTYIFAVLLACVVFHSGAQEKNYTIREEMPENVLIGDLLKDLNLSLIPNKSLTTA 60 V. 1 : 61 MQFKLVYKTGDVPLIRIEEDTGEIFTTGARIDREKLCAGIPRDEHCFYEVEVAILPDEIF 120 MQFKLVYKTGDVPLIRIEEDTGEIFTTGARIDREKLCAGIPRDEHCFYEVEVAILPDEIF V. 5 : 61 MQFKLVYKTGDVPLIRIEEDTGEIFTTGARIDREKLCAGIPRDEHCFYEVEVAILPDEIF 120 V. 1 : 121 RLVKIRFLIEDINDNAPLFPATVINISIPENSAINSKYTLPAAVDPDVGINGVQNYELIK 180 RLVKIRFLIEDINDNAPLFPATVINISIPENSAINSKYTLPAAVDPDVGINGVQNYELIK V. 5 : 121 RLVKIRFLIEDINDNAPLFPATVINISIPENSAINSKYTLPAAVDPDVGINGVQNYELIK 180 V. 1 181 SQNIFGLDVIETPEGDKMPQLIVQKELDREEKDTYVMKVKVEDGGFPQRSSTAILQVSVT 240 SQNIFGLDVIETPEGDKMPQLIVQKELDREEKDTYVMKVKVEDGGFPQRSSTAILQVSVT V. 5 : 181 SQNIFGLDVIETPEGDKMPQLIVQKELDREEKDTYVMKVKVEDGGFPQRSSTAILQVSVT 240 V. 1 : 241 DTNDNHPVFKETEIEVSIPENAPVGTSVTQLHATDADIGENAKIHFSFSNLVSNIARRLF 300 DTNDNHPVFKETEIEVSIPENAPVGTSVTQLHATDADIGENAKIHFSFSNLVSNIARRLF V. 5 : 241 DTNDNHPVFKETEIEVSIPENAPVGTSVTQLHATDADIGENAKIHFSFSNLVSNIARRLF 300 V. 1 301 HLNATTGLITIKEPLDREETPNHKLLVLASDGGLMPARAMVLVNVTDVNDNVPSIDIRYI 360 HLNATTGLITIKEPLDREETPNHKLLVLASDGGLMPARAMVLVNVTDVNDNVPSIDIRYI V. 5 : 301 HLNATTGLITIKEPLDREETPNHKLLVLASDGGLMPARAMVLVNVTDVNDNVPSIDIRYI 360 V. 1 : 361 VNPVNDTWLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLET 420 VNPVNDTVVLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLET V. 5 : 361 VNPVNDTVVLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLET 420 V. 1 : 421 AAYLDYESTKEYAIKLLAADAGKPPLNQSAMLFIKVKDENDNAPVFTQSFVTVSIPENNS 480 AAYLDYESTKEYAIKLLAADAGKPPLNQSAMLFIKVKDENDNAPVFTQSFVTVSIPENNS V. 5 : 421 AAYLDYESTKEYAIKLLAADAGKPPLNQSAMLFIKVKDENDNAPVFTQSFVTVSIPENNS 480 V. 1 : 481 PGIQLTKVSAMDADSGPNAKINYLLGPDAPPEFSLDCRTGMLTWKKLDREKEDKYLFTI 540 PGIQLTKVSAMDADSGPNAKINYLLGPDAPPEFSLDCRTGMLTWKKLDREKEDKYLFTI V. 5 : 481 PGIQLTKVSAMDADSGPNAKINYLLGPDAPPEFSLDCRTGMLTWKKLDREKEDKYLFTI 540 V. 1 : 541 LAKDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEYNFYVPENLPRHGTVGLITVTDPDYG 600 LAKDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEYNFYVPENLPRHGTVGLITVTDPDYG V. 5 : 541 LAKDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEYNFYVPENLPRHGTVGLITVTDPDYG 600 V. 1 : 601 DNSAVTLSILDENDDFTIDSQTGVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVT 660 DNSAVTLSILDENDDFTIDSQTGVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVT V. 5 : 601 DNSAVTLSILDENDDFTIDSQTGVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVT 660 V. 1 : 661 INWDVNDNKPVFIVPPSNCSYELVLPSTNPGTWFQVIAVDNDTGMNAEVRYSIVGGNT 720 INWDVNDNKPVFIVPPSNCSYELVLPSTNPGTWFQVIAVDNDTGMNAEVRYSIVGGNT V. 5 : 661 INWDVNDNKPVFIVPPSNCSYELVLPSTNPGTVVFQVIAVDNDTGMNAEVRYSIVGGNT 720 V. 1 : 721 RDLFAIDQETGNITLMEKCDVTDLGLHRVLVKANDLGQPDSLFSWIVNLFVNESVTNAT 780 RDLFAIDQETGNITLMEKCDVTDLGLHRVLVKANDLGQPDSLFSWIVNLFVNESVTNAT V. 5 : 721 RDLFAIDQETGNITLMEKCDVTDLGLHRVLVKANDLGQPDSLFSVVIVNLFVNESVTNAT 780 V. I : 781 LINELVRKSTEAPVTPNTEIADVSSPTSDYVKILVAAVAGTITWWIFITAWRCRQAP 840 LINELVRKSTEAPVTPNTEIADVSSPTSDYVKILVAAVAGTITWWIFITAWRCRQAP V. 5 : 781 LINELVRKSTEAPVTPNTEIADVSSPTSDYVKILVAAVAGTITWWIFITAWRCRQAP 840 V. 1 : 841 HLKAAQKNKQNSEWATPNPENRQMIMMKKKKKKKKHSPKNLLLNFVTIEETKADDVDSDG 900 HLKAAQKNKQNSEWATPNPENRQMIMMKKKKKKKKHSPKNLLLNFVTIEETKADDVDSDG V. 5 : 841 HLKAAQKNKQNSEWATPNPENRQMIMMKKKKKKKKHSPKNLLLNFVTIEETKADDVDSDG 900 V. 1 : 901 NRVTLDLPIDLEEQTMGKYNWVTTPTTFKPDSPDLARHYKSASPQPAFQIQPETPLNSKH 960 NRVTLDLPIDLEEQTMGKYNWVTTPTTFKPDSPDLARHYKSASPQPAFQIQPETPLNSKH V. 5 : 901 NRVTLDLPIDLEEQTMGKYNWVTTPTTFKPDSPDLARHYKSASPQPAFQIQPETPLNSKH 960 V. 1 : 961 HIIQELPLDNTFVACDSISKCSSSSSDPYSVSDCGYPVTTFEVPVSVHTRP 1011 HIIQELPLDNTFVACDSISKCSSSSSDPYSVSDCGYPVTTFEVPVSVHTRP V. 5 : 961 HIIQELPLDNTFVACDSISKCSSSSSDPYSVSDCGYPVTTFEVPVSVHTRP 1011 Table LII (e). Nucleotide sequence of transcript variant 109P1D4 v. 6 (SEQ ID NO : 261) ggcagtcggc gaactgtctg ggcgggagga gccgtgagca gtagctgcac tcagctgccc 60 gcgcggcaaa gaggaaggca agccaaacag agtgcgcaga gtggcagtgc cagcggcgac 120 acaggcagca caggcagccc gggctgcctg aatagcctca gaaacaacct cagcgactcc 180 ggctgctctg cggactgcga gctgtggcgg tagagcccgc tacagcagtc gcagtctccg 240 tggagcgggc ggaagccttt tttctccctt tcgtttacct cttcattcta ctctaaaggc 300 atcgttatta gagggtgctt aaaaagtaca gatcaactgg atggatgaat ggatggaaga 360 ggatggaata tcttaacaaa acacattttc cttaagtaaa ttcatgcata ctccaaataa 420 aatacagaat gtgaagtatc tctgaactgt gctgttgaat atggtagcta ctagctacat 480 gaaaatcctg ttgtgaataa gaaggattcc acagatcaca taccagagcg gttttgcctc 540 agctgctctc aactttgtaa tcttgtgaag aagctgacaa gcttggctga ttgcagtgca 600 ctatgaggac tgaatgacag tgggttttaa ttcagatatt tcaagtgttg tgcgggttaa 660 tacaacaaac tgtcacaagt gtttgttgtc cgggacgtac attttcgcgg tcctgctagt 720 atgcgtggtg ttccactctg gcgcccagga gaaaaactac accatccgag aagaaattcc 780 agaaaacgtc ctgataggca acttgttgaa agaccttaac ttgtcgctga ttccaaacaa 840 gtccttgaca actactatgc agttcaagct agtgtacaag accggagatg tgccactgat 900 tcgaattgaa gaggatactg gtgagatctt cactaccggc gctcgcattg atcgtgagaa 960 attatgtgct ggtatcccaa gggatgagca ttgcttttat gaagtggagg ttgccatttt 1020 gccggatgaa atatttagac tggttaagat acgttttctg atagaagata taaatgataa 1080 tgcaccattg ttcccagcaa cagttatcaa catatcaatt ccagagaact cggctataaa 1140 ctctaaatat actctcccag cggctgttga tcctgacgta ggcataaacg gagttcaaaa 1200 ctacgaacta attaagagtc aaaacatttt tggcctcgat gtcattgaaa caccagaagg 1260 agacaagatg ccacaactga ttgttcaaaa ggagttagat agggaagaga aggataccta 1320 tgtgatgaaa gtaaaggttg aagatggtgg ctttcctcaa agatccagta ctgctatttt 1380 gcaagtaagt gttactgata caaatgacaa ccacccagtc tttaaggaga cagagattga 1440 agtcagtata ccagaaaatg ctcctgtagg cacttcagtg acacagctcc atgccacaga 1500 tgctgacata ggtgaaaatg ccaagatcca cttctctttc agcaatctag tctccaacat 1560 tgccaggaga ttatttcacc tcaatgccac cactggactt atcacaatca aagaaccact 1620 ggatagggaa gaaacaccaa accacaagtt actggttttg gcaagtgatg gtggattgat 1680 gccagcaaga gcaatggtgc tggtaaatgt tacagatgtc aatgataatg tcccatccat 1740 tgacataaga tacatcgtca atcctgtcaa tgacacagtt gttctttcag aaaatattcc 1800 actcaacacc aaaattgctc tcataactgt gacggataag gatgcggacc ataatggcag 1860 ggtgacatgc ttcacagatc atgaaattcc tttcagatta aggccagtat tcagtaatca 1920 gttcctcctg gagaatgcag catatcttga ctatgagtcc acaaaagaat atgccattaa 1980 attactggct gcagatgctg gcaaacctcc tttgaatcag tcagcaatgc tcttcatcaa 2040 agtgaaagat gaaaatgaca atgctccagt tttcacccag tctttcgtaa ctgtttctat 2100 tcctgagaat aactctcctg gcatccagtt gatgaaagta agtgcaacgg atgcagacag 2160 tgggcctaat gctgagatca attacctgct aggccctgat gctccacctg aattcagcct 2220 ggatcgtcgt acaggcatgc tgactgtagt gaagaaacta gatagagaaa aagaggataa 2280 atatttattc acaattctgg caaaagataa tggggtacca cccttaacca gcaatgtcac 2340 agtctttgta agcattattg atcagaatga caatagccca gttttcactc acaatgaata 2400 caaattctat gtcccagaaa accttccaag gcatggtaca gtaggactaa tcactgtaac 2460 tgatcctgat tatggagaca attctgcagt tacgctctcc attttagatg agaatgatga 2520 cttcaccatt gattcacaaa ctggtgtcat ccgaccaaat atttcatttg atagagaaaa 2580 acaagaatct tacactttct atgtaaaggc tgaggatggt ggtagagtat cacgttcttc 2640 aagtgccaaa gtaaccataa atgtggttga tgtcaatgac aacaaaccag ttttcattgt 2700 ccctccttac aactattctt atgaattggt tctaccgtcc actaatccag gcacagtggt 2760 ctttcaggta attgctgttg acaatgacac tggcatgaat gcagaggttc gttacagcat 2820 tgtaggagga aacacaagag atctgtttgc aatcgaccaa gaaacaggca acataacatt 2880 gatggagaaa tgtgatgtta cagaccttgg tttacacaga gtgttggtca aagctaatga 2940 cttaggacag cctgattctc tcttcagtgt tgtaattgtc aatctgttcg tgaatgagtc 3000 agtgaccaat gctacactga ttaatgaact ggtgcgcaaa agcattgaag caccagtgac 3060 cccaaatact gagatagctg atgtatcctc accaactagt gactatgtca agatcctggt 3120 tgcagctgtt gctggcacca taactgtcgt tgtagttatt ttcatcactg ctgtagtaag 3180 atgtcgccag gcaccacacc ttaaggctgc tcagaaaaac atgcagaatt ctgaatgggc 3240 taccccaaac ccagaaaaca ggcagatgat aatgatgaag aaaaagaaaa agaagaagaa 3300 gcattcccct aagaacctgc tgcttaattt tgtcactatt gaagaaacta aggcagatga 3360 tgttgacagt gatggaaaca gagtcacact agaccttcct attgatctag aagagcaaac 3420 aatgggaaag tacaattggg taactacacc tactactttc aagcctgaca gccctgattt 3480 ggcccgacac tacaaatctg cctctccaca gcctgccttc caaattcagc ctgaaactcc 3540 cctgaatttg aagcaccaca tcatccaaga actgcctctc gataacacct ttgtggcctg 3600 tgactctatc tccaagtgtt cctcaagcag ttcagatccc tacagcgttt ctgactgtgg 3660 ctatccagtg acaaccttcg aggtacctgt gtccgtacac accagaccga ctgattccag 3720 gacatgaact attgaaatct gcagtgagat gtaactttct aggaacaaca aaattccatt 3780 ccccttccaa aaaatttcaa tggattgtga tttcaaaatt aggctaagat cattaatttt 3840 gtaatctaga tttcccatta taaaagcaag caaaaatcat cttaaaaatg atgtcctagt 3900 gaaccttgtg ctttctttag ctgtaatctg gcaatggaaa tttaaaattt atggaagaga 3960 cagtgcagca caataacaga gtactctcat gctgtttctc tgtttgctct gaatcaacag 4020 ccatgatgta atataaggct gtcttggtgt atacacttat ggttaatata tcagtcatga 4080 aacatgcaat tacttgccct gtctgattgt tgaataatta aaacattatc ttccaggagt 4140 ttggaagtga gctgaactag ccaaactact ctctgaaagg tatccagggc aagagacatt 4200 tttaagaccc caaacaaaca aaaaacaaaa ccaaaacact ctggttcagt gttttgaaaa 4260 tattcactaa cataatattg ctgagaaaat catttttatt acccaccact ctgcttaaaa 4320 gttgagtggg ccgggcgcgg tggctcacgc ctgtaatccc agcactttgg gaggccgagg 4380 cgggtggatc acgaggtcag gagattgaga ccatcctggc taacacggtg aaaccccatc 4440 tccactaaaa atacaaaaaa ttagcctggc gtggtggcgg gcgcctgtag tcccagctac 4500 tcgggaggct gaggcaggag aatagcgtga acccgggagg cggagcttgc agtgagccga 4560 gatggcgcca ctctgcactc cagcctgggt gacagagcaa gactctgtct caaaaagaaa 4620 aaaatgttca atgatagaaa ataattttac taggttttta tgttgattgt actcatggtg 4680 ttccactcct tttaattatt aaaaagttat ttttggggtg ggtgtggtgg ctcacaccgt 4740 aatcccagca ctttgggagg ccgaggtggg tggatcacct gaggtcagga gttcaagacc 4800 agtntggcca acatggcgaa accccgtttt 4830 Table LIII (e). Nucleotide sequence alignment of 109P1D4 v. 1 (SEQ ID NO : 262) and 109P1D4 v. 6 (SEQ ID NO : 263) Score = 5676 bits (2952), Expect = O. Oldentities = 3002/3027 (99%) Strand = Plus/Plus V. 1 : 852 ttgttgtccgggacgtacattttcgcggtcctgctagcatgcgtggtgttccactctggc 911 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII IIIIIIIIIIIIIIIIIIIIII V. 6 : 683 ttgttgtccgggacgtacattttcgcggtcctgctagtatgcgtggtgttccactctggc 742 V. 1 : 912 gcccaggagaaaaactacaccatccgagaagaaatgccagaaaacgtcctgataggcgac 971 Illllllllllllllllllllllllllllllllll IIIIIIIIIIIIIIIIIIIII II V. 6 : 743 gcccaggagaaaaactacaccatccgagaagaaattccagaaaacgtcctgataggcaac 802 V. 1 : 972 ttgttgaaagaccttaacttgtcgctgattccaaacaagtccttgacaactgctatgcag 1031 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII IIIIIIII V. 6 : 803 ttgttgaaagaccttaacttgtcgctgattccaaacaagtccttgacaactactatgcag 862 V. 1 : 1032 ttcaagctagtgtacaagaccggagatgtgccactgattcgaattgaagaggatactggt 1091 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 6 : 863 ttcaagctagtgtacaagaccggagatgtgccactgattcgaattgaagaggatactggt 922 V. 1 : 1092 gagatcttcactactggcgctcgcattgatcgtgagaaattatgtgctggtatcccaagg 1151 IIIIIIIIIIIIII IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 6 : 923 gagatcttcactaccggcgctcgcattgatcgtgagaaattatgtgctggtatcccaagg 982 V. 1 : 1152 gatgagcattgcttttatgaagtggaggttgccattttgccggatgaaatatttagactg 1211 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 6 : 983 gatgagcattgcttttatgaagtggaggttgccattttgccggatgaaatatttagactg 1042 V. 1 : 1212 gttaagatacgttttctgatagaagatataaatgataatgcaccattgttcccagcaaca 1271 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 6 : 1043 gttaagatacgttttctgatagaagatataaatgataatgcaccattgttcccagcaaca 1102 V. 1 : 1272 gttatcaacatatcaattccagagaactcggctataaactctaaatatactctcccagcg 1331 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 6 : 1103 gttatcaacatatcaattccagagaactcggctataaactctaaatatactctcccagcg 1162 V. 1 : 1332 gctgttgatcctgacgtaggaataaacggagttcaaaactacgaactaattaagagtcaa 1391 IIIIIIIIIIIIIIIIIIII IIIIIIIIIIIIIilllllllllllllllllllllllll V. 6 : 1163 gctgttgatcctgacgtaggcataaacggagttcaaaactacgaactaattaagagtcaa 1222 V. 1 : 1392 aacatttttggcctcgatgtcattgaaacaccagaaggagacaagatgccacaactgatt 1451 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 6 : 1223 aacatttttggcctcgatgtcattgaaacaccagaaggagacaagatgccacaactgatt 1282 V. 1 : 1452 gttcaaaaggagttagatagggaagagaaggatacctacgtgatgaaagtaaaggttgaa 1511 11111111111111111111111111111111111111 Illlllllllllllllllill V. 6 : 1283 gttcaaaaggagttagatagggaagagaaggatacctatgtgatgaaagtaaaggttgaa 1342 V. 1 : 1512 gatggtggctttcctcaaagatccagtactgctattttgcaagtgagtgttactgataca 1571 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII IIIIIIIIIIIIIII V. 6 : 1343 gatggtggctttcctcaaagatccagtactgctattttgcaagtaagtgttactgataca 1402 V. 1 : 1572 aatgacaaccacccagtctttaaggagacagagattgaagtcagtataccagaaaatgct 1631 Illllllllllllllllllllllllllllllllllllllllllllllllllillllllll V. 6 : 1403 aatgacaaccacccagtctttaaggagacagagattgaagtcagtataccagaaaatgct 1462 V. 1 : 1632 cctgtaggcacttcagtgacacagctccatgccacagatgctgacataggtgaaaatgcc 1691 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 6 : 1463 cctgtaggcacttcagtgacacagctccatgccacagatgctgacataggtgaaaatgcc 1522 V. 1 : 1692 aagatccacttctctttcagcaatctagtctccaacattgccaggagattatttcacctc 1751 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 6 : 1523 aagatccacttctctttcagcaatctagtctccaacattgccaggagattatttcacctc 1582 V. 1 : 1752 aatgccaccactggacttatcacaatcaaagaaccactggatagggaagaaacaccaaac 1811 Illlllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 6 : 1583 aatgccaccactggacttatcacaatcaaagaaccactggatagggaagaaacaccaaac 1642 V. 1 : 1812 cacaagttactggttttggcaagtgatggtggattgatgccagcaagagcaatggtgctg 1871 IIIIllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 6 : 1643 cacaagttactggttttggcaagtgatggtggattgatgccagcaagagcaatggtgctg 1702 V. 1 : 1872 gtaaatgttacagatgtcaatgataatgtcccatccattgacataagatacatcgtcaat 1931 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 6 : 1703 gtaaatgttacagatgtcaatgataatgtcccatccattgacataagatacatcgtcaat 1762 V. 1 : 1932 cctgtcaatgacacagttgttctttcagaaaatattccactcaacaccaaaattgctctc 1991 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 6 : 1763 cctgtcaatgacacagttgttctttcagaaaatattccactcaacaccaaaattgctctc 1822 V. 1 : 1992 ataactgtgacggataaggatgcggaccataatggcagggtgacatgcttcacagatcat 2051 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 6 : 1823 ataactgtgacggataaggatgcggaccataatggcagggtgacatgcttcacagatcat 1882 V. 1 : 2052 gaaatccctttcagattaaggccagtattcagtaatcagttcctcctggagactgcagca 2111 IIIII llllllllllllllllllllllllllllllllllllllllllllll IIIIIII V. 6 : 1883 gaaattcctttcagattaaggccagtattcagtaatcagttcctcctggagaatgcagca 1942 V. 1 : 2112 tatcttgactatgagtccacaaaagaatatgccattaaattactggctgcagatgctggc 2171 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 6 : 1943 tatcttgactatgagtccacaaaagaatatgccattaaattactggctgcagatgctggc 2002 V. 1 : 2172 aaacctcctttgaatcagtcagcaatgctcttcatcaaagtgaaagatgaaaatgacaat 2231 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 6 2003 aaacctcctttgaatcagtcagcaatgctcttcatcaaagtgaaagatgaaaatgacaat 2062 V. 1 : 2232 gctccagttttcacccagtctttcgtaactgtttctattcctgagaataactctcctggc 2291 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 6 : 2063 gctccagttttcacccagtctttcgtaactgtttctattcctgagaataactctcctggc 2122 V. 1 : 2292 atccagttgacgaaagtaagtgcaatggatgcagacagtgggcctaatgctaagatcaat 2351 IIIIIIIIII IIIIIIIIIIIIII Illllllllllllllllllllllll llllllll V. 6 : 2123 atccagttgatgaaagtaagtgcaacggatgcagacagtgggcctaatgctgagatcaat 2182 V. 1 : 2352 tacctgctaggccctgatgctccacctgaattcagcctggattgtcgtacaggcatgctg 2411 Illllllllllllllllllllllllllllllllfllllllll lllllllllllllllll V. 6 : 2183 tacctgctaggccctgatgctccacctgaattcagcctggatcgtcgtacaggcatgctg 2242 V. 1 : 2412 actgtagtgaagaaactagatagagaaaaagaggataaatatttattcacaattctggca 2471 Illlilllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 6 : 2243 actgtagtgaagaaactagatagagaaaaagaggataaatatttattcacaattctggca 2302 V. 1 : 2472 aaagataacggggtaccacccttaaccagcaatgtcacagtctttgtaagcattattgat 2531 IIIIIIII IIIIIIIIIIIIIIIIIIIIIIIIIilllllllllllllllllllllllll V. 6 : 2303 aaagataatggggtaccacccttaaccagcaatgtcacagtctttgtaagcattattgat 2362 V. 1 : 2532 cagaatgacaatagcccagttttcactcacaatgaatacaacttctatgtcccagaaaac 2591 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII IIIIIIIIIIIIIIIIII V. 6 : 2363 cagaatgacaatagcccagttttcactcacaatgaatacaaattctatgtcccagaaaac 2422 V. 1 : 2592 cttccaaggcatggtacagtaggactaatcactgtaactgatcctgattatggagacaat 2651 Illlllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 6 : 423 cttccaaggcatggtacagtaggactaatcactgtaactgatcctgattatggagacaat 2482 V. 1 : 2652 tctgcagttacgctctccattttagatgagaatgatgacttcaccattgattcacaaact 2711 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 6 : 2483 tctgcagttacgctctccattttagatgagaatgatgacttcaccattgattcacaaact 2542 V. 1 : 2712 ggtgtcatccgaccaaatatttcatttgatagagaaaaacaagaatcttacactttctat 2771 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 6 : 2543 ggtgtcatccgaccaaatatttcatttgatagagaaaaacaagaatcttacactttctat 2602 V. 1 : 2772 gtaaaggctgaggatggtggtagagtatcacgttcttcaagtgccaaagtaaccataaat 2831 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 6 : 2603 gtaaaggctgaggatggtggtagagtatcacgttcttcaagtgccaaagtaaccataaat 2662 V. 1 : 2832 gtggttgatgtcaatgacaacaaaccagttttcattgtccctccttccaactgttcttat 2891 m m m m m m m m m m m m m m m im n m m n V. 6 : 2663 gtggttgatgtcaatgacaacaaaccagttttcattgtccctccttacaactattcttat 2722 V. 1 : 2892 gaattggttctaccgtccactaatccaggcacagtggtctttcaggtaattgctgttgac 2951 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 6 : 2723 gaattggttctaccgtccactaatccaggcacagtggtctttcaggtaattgctgttgac 2782 V. 1 : 2952 aatgacactggcatgaatgcagaggttcgttacagcattgtaggaggaaacacaagagat 3011 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 6 : 2783 aatgacactggcatgaatgcagaggttcgttacagcattgtaggaggaaacacaagagat 2842 V. 1 : 3012 ctgtttgcaatcgaccaagaaacaggcaacataacattgatggagaaatgtgatgttaca 3071 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 6 : 2843 ctgtttgcaatcgaccaagaaacaggcaacataacattgatggagaaatgtgatgttaca 2902 V. 1 : 3072 gaccttggtttacacagagtgttggtcaaagctaatgacttaggacagcctgattctctc 3131 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 6 : 2903 gaccttggtttacacagagtgttggtcaaagctaatgacttaggacagcctgattctctc 2962 V. 1 : 3132 ttcagtgttgtaattgtcaatctgttcgtgaatgagtcggtgaccaatgctacactgatt 3191 Illllllllllllllllllllllllllllllllllll IIIIIIIIIIIIIIIIIIIII V. 6 : 2963 ttcagtgttgtaattgtcaatctgttcgtgaatgagtcagtgaccaatgctacactgatt 3022 V. 1 : 3192 aatgaactggtgcgcaaaagcactgaagcaccagtgaccccaaatactgagatagctgat 3251 IIIIIIIIIIIIIIIIIIIIII IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 6 : 3023 aatgaactggtgcgcaaaagcattgaagcaccagtgaccccaaatactgagatagctgat 3082 V. 1 : 3252 gtatcctcaccaactagtgactatgtcaagatcctggttgcagctgttgctggcaccata 3311 IIIIllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 6 : 3083 gtatcctcaccaactagtgactatgtcaagatcctggttgcagctgttgctggcaccata 3142 V. 1 : 3312 actgtcgttgtagttattttcatcactgctgtagtaagatgtcgccaggcaccacacctt 3371 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII - V. 6 : 3143 actgtcgttgtagttattttcatcactgctgtagtaagatgtcgccaggcaccacacctt 3202 V. 1 : 3372 aaggctgctcagaaaaacaagcagaattctgaatgggctaccccaaacccagaaaacagg 3431 IIIIIIIIIIIIIIIIIII Illlllllllllllllllllllllllllllllllllllll V. 6 : 3203 aaggctgctcagaaaaacatgcagaattctgaatgggctaccccaaacccagaaaacagg 3262 V. 1 : 3432 cagatgataatgatgaagaaaaagaaaaagaagaagaagcattcccctaagaacttgctg 3491 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIilllllllllllllllllll IIIII V. 6 : 3263 cagatgataatgatgaagaaaaagaaaaagaagaagaagcattcccctaagaacctgctg 3322 V. 1 : 3492 cttaattttgtcactattgaagaaactaaggcagatgatgttgacagtgatggaaacaga 3551 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 6 : 3323 cttaattttgtcactattgaagaaactaaggcagatgatgttgacagtgatggaaacaga 3382 V. 1 : 3552 gtcacactagaccttcctattgatctagaagagcaaacaatgggaaagtacaattgggta 3611 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 6 : 3383 gtcacactagaccttcctattgatctagaagagcaaacaatgggaaagtacaattgggta 3442 V. 1 : 3612 actacacctactactttcaagcccgacagccctgatttggcccgacactacaaatctgcc 3671 IIIIIIIIIIIIIIIIIIIIIII IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 6 : 3443 actacacctactactttcaagcctgacagccctgatttggcccgacactacaaatctgcc 3502 V. 1 : 3672 tctccacagcctgccttccaaattcagcctgaaactcccctgaattcgaagcaccacatc 3731 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII llllilllllll V. 6 : 3503 tctccacagcctgccttccaaattcagcctgaaactcccctgaatttgaagcaccacatc 3562 V. 1 : 3732 atccaagaactgcctctcgataacacctttgtggcctgtgactctatctccaagtgttcc 3791 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII111111111 V. 6 : 3563 atccaagaactgcctctcgataacacctttgtggcctgtgactctatctccaagtgttcc 3622 V. 1 : 3792 tcaagcagttcagatccctacagcgtttctgactgtggctatccagtgacgaccttcgag 3851 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII IIIIIIIII V. 6 : 3623 tcaagcagttcagatccctacagcgtttctgactgtggctatccagtgacaaccttcgag 3682 V. 1 : 3852 gtacctgtgtccgtacacaccagaccg 3878 IIIIIIIIIIIIIIIIIIIIIIIIIII V. 6 : 3683 gtacctgtgtccgtacacaccagaccg 3709 Table LIV (e). Peptide sequences of protein coded by 109P1D4 v. 6 (SEQ ID NO : 264) MTVGFNSDIS SVVRVNTTNC HKCLLSGTYI FAVLLVCVVF HSGAQEKNYT IREEIPENVL 60 IGNLLKDLNL SLIPNKSLTT TMQFKLVYKT GDVPLIRIEE DTGEIFTTGA RIDREKLCAG 120 IPRDEHCFYE VEVAILPDEI FRLVKIRFLI EDINDNAPLF PATVINISIP ENSAINSKYT 180 LPAAVDPDVG INGVQNYELI KSQNIFGLDV IETPEGDKMP QLIVQKELDR EEKDTYVMKV 240 KVEDGGFPQR SSTAILQVSV TDTNDNHPVF KETEIEVSIP ENAPVGTSVT QLHATDADIG 300 ENAKIHFSFS NLVSNIARRL FHLNATTGLI TIKEPLDREE TPNHKLLVLA SDGGLMPARA 360 MVLVNVTDVN DNVPSIDIRY IVNPVNDTVV LSENIPLNTK IALITVTDKD ADHNGRVTCF 420 TDHEIPFRLR PVFSNQFLLE NAAYLDYEST KEYAIKLLAA DAGKPPLNQS AMLFIKVKDE 480 NDNAPVFTQS FVTVSIPENN SPGIQLMKVS ATDADSGPNA EINYLLGPDA PPEFSLDRRT 540 GMLTVVKKLD REKEDKYLFT ILAKDNGVPP LTSNVTVFVS IIDQNDNSPV FTHNEYKFYV 600 PENLPRHGTV GLITVTDPDY GDNSAVTLSI LDENDDFTID SQTGVIRPNI SFDREKQESY 660 TFYVKAEDGG RVSRSSSAKV TINVVDVNDN KPVFIVPPYN YSYELVLPST NPGTVVFQVI 720 AVDNDTGMNA EVRYSIVGGN TRDLFAIDQE TGNITLMEKC DVTDLGLHRV LVKANDLGQP 780 DSLFSVVIVN LFVNESVTNA TLINELVRKS IEAPVTPNTE IADVSSPTSD YVKILVAAVA 840 GTITVVVVIF ITAVVRCRQA PHLKAAQKNM QNSEWATPNP ENRQMIMMKK KKKKKKHSPK 900 NLLLNFVTIE ETKADDVDSD GNRVTLDLPI DLEEQTMGKY NWVTTPTTFK PDSPDLARHY 960 KSASPQPAFQ IQPETPLNLK HHIIQELPLD NTFVACDSIS KCSSSSSDPY SVSDCGYPVT 1020 TFEVPVSVHT RPTDSRT 1037 Table LV (e). Amino acid sequence alignment of 109P1D4 v. 1 (SEQ ID NO : 265) and 109P1D4 v. 6 (SEQ ID NO : 266) Score = 1966 bits (5093), Expect = O. Oldentities = 994/1009 (98%), Positives = 997/1009 (98%) V. 1 : 3 LLSGTYIFAVLLACVVFHSGAQEKNYTIREEMPENVLIGDLLKDLNLSLIPNKSLTTAMQ 62 LLSGTYIFAVLL CWFHSGAQEKNYTIREE+PENVLIG+LLKDLNLSLIPNKSLTT MQ V. 6 : 24 LLSGTYIFAVLLVCWFHSGAQEKNYTIREEIPENVLIGNLLKDLNLSLIPNKSLTTTMQ 83 V. 1 : 63 FKLVYKTGDVPLIRIEEDTGEIFTTGARIDREKLCAGIPRDEHCFYEVEVAILPDEIFRL 122 FKLVYKTGDVPLIRIEEDTGEIFTTGARIDREKLCAGIPRDEHCFYEVEVAILPDEIFRL V. 6 : 84 FKLVYKTGDVPLIRIEEDTGEIFTTGARIDREKLCAGIPRDEHCFYEVEVAILPDEIFRL 143 V. 1 123 VKIRFLIEDINDNAPLFPATVINISIPENSAINSKYTLPAAVDPDVGINGVQNYELIKSQ 182 VKIRFLIEDINDNAPLFPATVINISIPENSAINSKYTLPAAVDPDVGINGVQNYELIKSQ V. 6 : 144 VKIRFLIEDINDNAPLFPATVINISIPENSAINSKYTLPAAVDPDVGINGVQNYELIKSQ 203 V. 1 : 183 NIFGLDVIETPEGDKMPQLIVQKELDREEKDTYVMKVKVEDGGFPQRSSTAILQVSVTDT 242 NIFGLDVIETPEGDKMPQLIVQKELDREEKDTYVMKVKVEDGGFPQRSSTAILQVSVTDT V. 6 : 204 NIFGLDVIETPEGDKMPQLIVQKELDREEKDTYVMKVKVEDGGFPQRSSTAILQVSVTDT 263 V. 1 : 243 NDNHPVFKETEIEVSIPENAPVGTSVTQLHATDADIGENAKIHFSFSNLVSNIARRLFHL 302 NDNHPVFKETEIEVSIPENAPVGTSVTQLHATDADIGENAKIHFSFSNLVSNIARRLFHL V. 6 : 264 NDNHPVFKETEIEVSIPENAPVGTSVTQLHATDADIGENAKIHFSFSNLVSNIARRLFHL 323 V. 1 : 303 NATTGLITIKEPLDREETPNHKLLVLASDGGLMPARAMVLVNVTDVNDNVPSIDIRYIVN 362 NATTGLITIKEPLDREETPNHKLLVLASDGGLMPARAMVLVNVTDVNDNVPSIDIRYIVN V. 6 : 324 NATTGLITIKEPLDREETPNHKLLVLASDGGLMPARAMVLVNVTDVNDNVPSIDIRYIVN 383 V. 1 : 363 PVNDTWLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLETAA 422 PVNDTWLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLE AA V. 6 : 384 PVNDTWLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLENAA 443 V. 1 : 423 YLDYESTKEYAIKLLAADAGKPPLNQSAMLFIKVKDENDNAPVFTQSFVTVSIPENNSPG 482 YLDYESTKEYAIKLLAADAGKPPLNQSAMLFIKVKDENDNAPVFTQSFVTVSIPENNSPG V. 6 : 444 YLDYESTKEYAIKLLAADAGKPPLNQSAMLFIKVKDENDNAPVFTQSFVTVSIPENNSPG 503 V. 1 : 483 IQLTKVSAMDADSGPNAKINYLLGPDAPPEFSLDCRTGMLTWKKLDREKEDKYLFTILA 542 IQL KVSA DADSGPNA+INYLLGPDAPPEFSLD RTGMLTWKKLDREKEDKYLFTILA V. 6 : 504 IQLMKVSATDADSGPNAEINYLLGPDAPPEFSLDRRTGMLTWKKLDREKEDKYLFTILA 563 V. 1 : 543 KDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEYNFYVPENLPRHGTVGLITVTDPDYGDN 602 KDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEY FYVPENLPRHGTVGLITVTDPDYGDN V. 6 : 564 KDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEYKFYVPENLPRHGTVGLITVTDPDYGDN 623 V. 1 : 603 SAVTLSILDENDDFTIDSQTGVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVTIN 662 SAVTLSILDENDDFTIDSQTGVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVTIN V. 6 : 624 SAVTLSILDENDDFTIDSQTGVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVTIN 683 V. 1 : 663 VVDVNDNKPVFIVPPSNCSYELVLPSTNPGTWFQVIAVDNDTGMNAEVRYSIVGGNTRD 722 WDVNDNKPVFIVPP N SYELVLPSTNPGTWFQVIAVDNDTGMNAEVRYSIVGGNTRD V. 6 : 684 WDVNDNKPVFIVPPYNYSYELVLPSTNPGTWFQVIAVDNDTGMNAEVRYSIVGGNTRD 743 V. 1 : 723 LFAIDQETGNITLMEKCDVTDLGLHRVLVKANDLGQPDSLFSWIVNLFVNESVTNATLI 782 LFAIDQETGNITLMEKCDVTDLGLHRVLVKANDLGQPDSLFSWIVNLFVNESVTNATLI V. 6 : 744 LFAIDQETGNITLMEKCDVTDLGLHRVLVKANDLGQPDSLFSWIVNLFVNESVTNATLI 803 V. 1 : 783 NELVRKSTEAPVTPNTEIADVSSPTSDYVKILVAAVAGTITVWVIFITAVVRCRQAPHL 842 NELVRKS EAPVTPNTEIADVSSPTSDYVKILVAAVAGTITVVWIFITAVVRCRQAPHL V. 6 : 804 NELVRKSIEAPVTPNTEIADVSSPTSDYVKILVAAVAGTITWWIFITAWRCRQAPHL 863 V. 1 : 843 KAAQKNKQNSEWATPNPENRQMIMMKKKKKKKKHSPKNLLLNFVTIEETKADDVDSDGNR 902 KAAQKN QNSEWATPNPENRQMIMMKKKKKKKKHSPKNLLLNFVTIEETKADDVDSDGNR V. 6 : 864 KAAQKNMQNSEWATPNPENRQMIMMKKKKKKKKHSPKNLLLNFVTIEETKADDVDSDGNR 923 V. 1 : 903 VTLDLPIDLEEQTMGKYNWVTTPTTFKPDSPDLARHYKSASPQPAFQIQPETPLNSKHHI 962 VTLDLPIDLEEQTMGKYNWVTTPTTFKPDSPDLARHYKSASPQPAFQIQPETPLN KHHI V. 6 : 924 VTLDLPIDLEEQTMGKYNWVTTPTTFKPDSPDLARHYKSASPQPAFQIQPETPLNLKHHI 983 V. 1 : 963 IQELPLDNTFVACDSISKCSSSSSDPYSVSDCGYPVTTFEVPVSVHTRP 1011 IQELPLDNTFVACDSISKCSSSSSDPYSVSDCGYPVTTFEVPVSVHTRP V. 6 : 984 IQELPLDNTFVACDSISKCSSSSSDPYSVSDCGYPVTTFEVPVSVHTRP 1032 Table LII(f). Nucleotide sequence of transcript variant 109P1D4 v.7 (SEQ ID NO : 267) ggtggtccag tacctccaaa gatatggaat acactcctga aatatcctga aacctttttt 60 ttttcagaat cctttaataa gcagttatgt caatctgaaa gttgcttact tgtactttat 120 attaatagct attcttgttt ttcttatcca aagaaaaatc ctctaatccc cttttcacat 180 gatagttgtt accatgttta ggcgttagtc acatcaaccc ctctcctctc ccaaacttct 240 cttcttcaaa tcaaacttta ttagtccctc ctttataatg attccttgcc tccttttatc 300 cagatcaatt ttttttcact ttgatgccca gagctgaaga aatggactat tgtataaatt 360 attcattgcc aagagaataa ttgcatttta aacccatgtt ataacaaaga ataatgatta 420 tattttgtga tttgtaacaa atacccttta ttttccctta actattgaat taaatatttt 480 aattatttgt attctcttta actatcttgg tatattaaag tattatcttt tatatattta 540 tcaatggtgg acacttttat aggtactctg tgtcattttt gatactgtag gtatcttatt 600 tcatttatct ttattcttaa tgtacgaatt cataatattt gattcagaac agatttatca 660 ctaattaaca gagtgtcaat tatgctaaca tctcatttac tgattttaat ttaaaacagt 720 ttttgttaac atgcatgttt agggttggct tcttaataat ttcttcttcc tcttctctct 780 ctcctcttct tttggtcagt gttgtgcggg ttaatacaac aaactgtcac aagtgtttgt 840 tgtccgggac gtacattttc gcggtcctgc tagtatgcgt ggtgttccac tctggcgccc 900 aggagaaaaa ctacaccatc cgagaagaaa ttccagaaaa cgtcctgata ggcaacttgt 960 tgaaagacct taacttgtcg ctgattccaa acaagtcctt gacaactact atgcagttca 1020 agctagtgta caagaccgga gatgtgccac tgattcgaat tgaagaggat actggtgaga 1080 tcttcactac cggcgctcgc attgatcgtg agaaattatg tgctggtatc ccaagggatg 1140 agcattgctt ttatgaagtg gaggttgcca ttttgccgga tgaaatattt agactggtta 1200 agatacgttt tctgatagaa gatataaatg ataatgcacc attgttccca gcaacagtta 1260 tcaacatatc aattccagag aactcggcta taaactctaa atatactctc ccagcggctg 1320 ttgatcctga cgtaggcata aacggagttc aaaactacga actaattaag agtcaaaaca 1380 tttttggcct cgatgtcatt gaaacaccag aaggagacaa gatgccacaa ctgattgttc 1440 aaaaggagtt agatagggaa gagaaggata cctatgtgat gaaagtaaag gttgaagatg 1500 gtggctttcc tcaaagatcc agtactgcta ttttgcaagt aagtgttact gatacaaatg 1560 acaaccaccc agtctttaag gagacagaga ttgaagtcag tataccagaa aatgctcctg 1620 taggcacttc agtgacacag ctccatgcca cagatgctga cataggtgaa aatgccaaga 1680 tccacttctc tttcagcaat ctagtctcca acattgccag gagattattt cacctcaatg 1740 ccaccactgg acttatcaca atcaaagaac cactggatag ggaagaaaca ccaaaccaca 1800 agttactggt tttggcaagt gatggtggat tgatgccagc aagagcaatg gtgctggtaa 1860 atgttacaga tgtcaatgat aatgtcccat ccattgacat aagatacatc gtcaatcctg 1920 tcaatgacac agttgttctt tcagaaaata ttccactcaa caccaaaatt gctctcataa 1980 ctgtgacgga taaggatgcg gaccataatg gcagggtgac atgcttcaca gatcatgaaa 2040 ttcctttcag attaaggcca gtattcagta atcagttcct cctggagaat gcagcatatc 2100 ttgactatga gtccacaaaa gaatatgcca ttaaattact ggctgcagat gctggcaaac 2160 ctcctttgaa tcagtcagca atgctcttca tcaaagtgaa agatgaaaat gacaatgctc 2220 cagttttcac ccagtctttc gtaactgttt ctattcctga gaataactct cctggcatcc 2280 agttgatgaa agtaagtgca acggatgcag acagtgggcc taatgctgag atcaattacc 2340 tgctaggccc tgatgctcca cctgaattca gcctggatcg tcgtacaggc atgctgactg 2400 tagtgaagaa actagataga gaaaaagagg ataaatattt attcacaatt ctggcaaaag 2460 ataatggggt accaccctta accagcaatg tcacagtctt tgtaagcatt attgatcaga 2520 atgacaatag cccagttttc actcacaatg aatacaaatt ctatgtccca gaaaaccttc 2580 caaggcatgg tacagtagga ctaatcactg taactgatcc tgattatgga gacaattctg 2640 cagttacgct ctccatttta gatgagaatg atgacttcac cattgattca caaactggtg 2700 tcatccgacc aaatatttca tttgatagag aaaaacaaga atcttacact ttctatgtaa 2760 aggctgagga tggtggtaga gtatcacgtt cttcaagtgc caaagtaacc ataaatgtgg 2820 ttgatgtcaa tgacaacaaa ccagttttca ttgtccctcc ttacaactat tcttatgaat 2880 tggttctacc gtccactaat ccaggcacag tggtctttca ggtaattgct gttgacaatg 2940 acactggcat gaatgcagag gttcgttaca gcattgtagg aggaaacaca agagatctgt 3000 ttgcaatcga ccaagaaaca ggcaacataa cattgatgga gaaatgtgat gttacagacc 3060 ttggtttaca cagagtgttg gtcaaagcta atgacttagg acagcctgat tctctcttca 3120 gtgttgtaat tgtcaatctg ttcgtgaatg agtcagtgac caatgctaca ctgattaatg 3180 aactggtgcg caaaagcatt gaagcaccag tgaccccaaa tactgagata gctgatgtat 3240 cctcaccaac tagtgactat gtcaagatcc tggttgcagc tgttgctggc accataactg 3300 tcgttgtagt tattttcatc actgctgtag taagatgtcg ccaggcacca caccttaagg 3360 ctgctcagaa aaacatgcag aattctgaat gggctacccc aaacccagaa aacaggcaga'3420 tgataatgat gaagaaaaag aaaaagaaga agaagcattc ccctaagaac ctgctgctta 3480 atgttgtcac tattgaagaa actaaggcag atgatgttga cagtgatgga aacagagtca 3540 cactagacct tcctattgat ctagaagagc aaacaatggg aaagtacaat tgggtaacta 3600 cacctactac tttcaagcct gacagccctg atttggcccg acactacaaa tctgcctctc 3660 cacagcctgc cttccaaatt cagcctgaaa ctcccctgaa tttgaagcac cacatcatcc 3720 aagaactgcc tctcgataac acctttgtgg cctgtgactc tatctccaat tgttcctcaa 3780 gcagttcaga tccctacagc gtttctgact gtggctatcc agtgacaacc ttcgaggtac 3840 ctgtgtccgt acacaccaga ccgactgatt ccaggacatg aactattgaa atctgcagtg 3900 agatgtaact ttctaggaac aacaaaattc cattcccctt ccaaaaaatt tcaatgattg 3960 tgatttcaaa attaggctaa gatcattaat tttgtaatct agatttccca ttataaaagc 4020 aagcaaaaat catcttaaaa atgatgtcct agtgaacctt gtgctttctt tagctgtaat 4080 ctggcaatgg aaatttaaaa tttatggaag agacagtgca gcgcaataac agagtactct 4140 catgctgttt ctctgtttgc tctgaatcaa cagccatgat gtaatataag gctgtcttgg 4200 tgtatacact tatggttaat atatcagtca tgaaacatgc aattacttgc cctgtctgat 4260 tgttgaataa ttaaaacatt atctccagga gtttggaagt gagctgaact agccaaacta 4320 ctctctgaaa ggtatccagg gcaagagaca tttttaagac cccaaacaaa caaaaaacaa 4380 aaccaaaaca ctctggttca gtgttttgaa aatattgact aacataatat tgctgagaaa 4440 atcattttta ttacccacca ctctgcttaa aagttgagtg ggccgggcgc ggtggctcac 4500 gcctgtaatt ccagcacttt gggaggccga ggcgggtgga tcacgaggtc aggatattga 4560 gaccatcctg gctaacatgg tgaaacccca tctccactaa aaatacaaaa aattagctgg 4620 gcgtggtggc gggcgcctgt agtcccagct actcgggagg ctgaggcagg agaatggcgt 4680 gaacccggga ggcggagctt gcagtgagcc gagatggcgc cactgcactc cagcctgggt 4740 gacagagcaa gactctgtct caaaaagaaa aaaatgttca gtgatagaaa ataattttac 4800 taggttttta tgttgattgt actcatgctg ttccactcct tttaattatt aaaaagttat 4860 ttttggctgg gtgtggtggc tcatacctgt aatcccagca ctttgggagg ccgaggcggg 4920 tggatcacct gaggtcagga gttcaagacc agtctggcca acat 4964 Table LIII(f). Nucleotide sequence alignment of 109P1 D4 v. 1 (SEQ ID NO : 268) and 109P1 D4 v. 7 (SEQ ID NO : 269) Score = 5664 bits (2946), Expect = O. Oldentities = 3000/3027 (99%) Strand = Plus/Plus V. 1 : 852 ttgttgtccgggacgtacattttcgcggtcctgctagcatgcgtggtgttccactctggc 911 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII IIIIIIIIIIIIIIIIIIIIII V. 7 : 37 ttgttgtccgggacgtacattttcgcggtcctgctagtatgcgtggtgttccactctggc 896 V. 1 : 912 gcccaggagaaaaactacaccatccgagaagaaatgccagaaaacgtcctgataggcgac 971 IIIIlllllllllllllllllllllllllllllll IIIIIIIIIIIIIIIIIIIII II V. 7 : 897 gcccaggagaaaaactacaccatccgagaagaaattccagaaaacgtcctgataggcaac 956 V. 1 : 972 ttgttgaaagaccttaacttgtcgctgattccaaacaagtccttgacaactgctatgcag 1031 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII IIIIIIII V. 7 : 957 ttgttgaaagaccttaacttgtcgctgattccaaacaagtccttgacaactactatgcag 1016 V. 1 : 1032 ttcaagctagtgtacaagaccggagatgtgccactgattcgaattgaagaggatactggt 1091 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 7 : 1017 ttcaagctagtgtacaagaccggagatgtgccactgattcgaattgaagaggatactggt 1076 V. 1 : 1092 gagatcttcactactggcgctcgcattgatcgtgagaaattatgtgctggtatcccaagg 1151 IIIIIIIIIIIIII IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 7 1077 gagatcttcactaccggcgctcgcattgatcgtgagaaattatgtgctggtatcccaagg 1136 V. 1 : 1152 gatgagcattgcttttatgaagtggaggttgccattttgccggatgaaatatttagactg 1211 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 7 : 1137 gatgagcattgcttttatgaagtggaggttgccattttgccggatgaaatatttagactg 1196 V. 1 : 1212 gttaagatacgttttctgatagaagatataaatgataatgcaccattgttcccagcaaca 1271 IIIIIIIIIIIIIIIIIIIIIIIIIIIIilllllllllllllllllllllllllllllll V. 7 1197 gttaagatacgttttctgatagaagatataaatgataatgcaccattgttcccagcaaca 1256 V. 1 : 1272 gttatcaacatatcaattccagagaactcggctataaactctaaatatactctcccagcg 1331 lllllllllllllllllllllllllllllllllllllllllllllllllllllllllill V. 7 : 1257 gttatcaacatatcaattccagagaactcggctataaactctaaatatactctcccagcg 1316 V. 1 : 1332 gctgttgatcctgacgtaggaataaacggagttcaaaactacgaactaattaagagtcaa 1391 IIIIIIIIIIIIIIIIIIII IIIIlllllllllllllllllllllllllllllllllll V. 7 : 1317 gctgttgatcctgacgtaggcataaacggagttcaaaactacgaactaattaagagtcaa 1376 V. 1 : 1392 aacatttttggcctcgatgtcattgaaacaccagaaggagacaagatgccacaactgatt 1451 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 7 : 1377 aacatttttggcctcgatgtcattgaaacaccagaaggagacaagatgccacaactgatt 1436 V. 1 : 1452 gttcaaaaggagttagatagggaagagaaggatacctacgtgatgaaagtaaaggttgaa 1511 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII IIIIIIIIIIIIIIIIIIIII V. 7 : 1437 gttcaaaaggagttagatagggaagagaaggatacctatgtgatgaaagtaaaggttgaa 1496 V. 1 : 1512 gatggtggctttcctcaaagatccagtactgctattttgcaagtgagtgttactgataca 1571 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII IIIIIIIIIIIIIII V. 7 : 1497 gatggtggctttcctcaaagatccagtactgctattttgcaagtaagtgttactgataca 1556 V. 1 : 1572 aatgacaaccacccagtctttaaggagacagagattgaagtcagtataccagaaaatgct 1631 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 7 : 1557 aatgacaaccacccagtctttaaggagacagagattgaagtcagtataccagaaaatgct 1616 V. 1 : 1632 cctgtaggcacttcagtgacacagctccatgccacagatgctgacataggtgaaaatgcc 1691 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 7 : 1617 cctgtaggcacttcagtgacacagctccatgccacagatgctgacataggtgaaaatgcc 1676 V. 1 : 1692 aagatccacttctctttcagcaatctagtctccaacattgccaggagattatttcacctc 1751 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 7 : 1677 aagatccacttctctttcagcaatctagtctccaacattgccaggagattatttcacctc 1736 V. 1 : 1752 aatgccaccactggacttatcacaatcaaagaaccactggatagggaagaaacaccaaac 1811 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 7 : 1737 aatgccaccactggacttatcacaatcaaagaaccactggatagggaagaaacaccaaac 1796 V. 1 : 1812 cacaagttactggttttggcaagtgatggtggattgatgccagcaagagcaatggtgctg 1871 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 7 : 1797 cacaagttactggttttggcaagtgatggtggattgatgccagcaagagcaatggtgctg 1856 V. 1 : 1872 gtaaatgttacagatgtcaatgataatgtcccatccattgacataagatacatcgtcaat 1931 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 7 : 1857 gtaaatgttacagatgtcaatgataatgtcccatccattgacataagatacatcgtcaat 1916 V. 1 : 1932 cctgtcaatgacacagttgttctttcagaaaatattccactcaacaccaaaattgctctc 1991 IIIIllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 7 : 1917 cctgtcaatgacacagttgttctttcagaaaatattccactcaacaccaaaattgctctc 1976 V. 1 : 1992 ataactgtgacggataaggatgcggaccataatggcagggtgacatgcttcacagatcat 2051 Illlllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 7 : 1977 ataactgtgacggataaggatgcggaccataatggcagggtgacatgcttcacagatcat 2036 V. 1 : 2052 gaaatccctttcagattaaggccagtattcagtaatcagttcctcctggagactgcagca 2111 IIIII IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII IIIIIII V. 7 : 2037 gaaattcctttcagattaaggccagtattcagtaatcagttcctcctggagaatgcagca 2096 V. 1 : 2112 tatcttgactatgagtccacaaaagaatatgccattaaattactggctgcagatgctggc 2171 111111111111111111111111111111111111111111111111111111111111 V. 7 : 2097 tatcttgactatgagtccacaaaagaatatgccattaaattactggctgcagatgctggc 2156 V. 1 : 2172 aaacctcctttgaatcagtcagcaatgctcttcatcaaagtgaaagatgaaaatgacaat 2231 Illlllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 7 : 2157 aaacctcctttgaatcagtcagcaatgctcttcatcaaagtgaaagatgaaaatgacaat 2216 V. 1 : 2232 gctccagttttcacccagtctttcgtaactgtttctattcctgagaataactctcctggc 2291 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 7 : 2217 gctccagttttcacccagtctttcgtaactgtttctattcctgagaataactctcctggc 2276 V. 1 : 2292 atccagttgacgaaagtaagtgcaatggatgcagacagtgggcctaatgctaagatcaat 2351 IIIIIIIIII IIIIIIIIIIIIII IIIIIIIIIIIIIIIIIIIIIIIII IIIIIIII V. 7 : 2277 atccagttgatgaaagtaagtgcaacggatgcagacagtgggcctaatgctgagatcaat 2336 V. 1 : 2352 tacctgctaggccctgatgctccacctgaattcagcctggattgtcgtacaggcatgctg 2411 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII IIIIIIIIIIIIIIIII V. 7 : 2337 tacctgctaggccctgatgctccacctgaattcagcctggatcgtcgtacaggcatgctg 2396 V. 1 : 2412 actgtagtgaagaaactagatagagaaaaagaggataaatatttattcacaattctggca 2471 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 7 : 2397 actgtagtgaagaaactagatagagaaaaagaggataaatatttattcacaattctggca 2456 V. 1 : 2472 aaagataacggggtaccacccttaaccagcaatgtcacagtctttgtaagcattattgat 2531 IIIIIIII IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 7 : 2457 aaagataatggggtaccacccttaaccagcaatgtcacagtctttgtaagcattattgat 2516 V. 1 : 2532 cagaatgacaatagcccagttttcactcacaatgaatacaacttctatgtcccagaaaac 2591 Illllllllllllllllllllllllllllllllllllllll IIIIIIIIIIIIIIIIII V. 7 : 2517 cagaatgacaatagcccagttttcactcacaatgaatacaaattctatgtcccagaaaac 2576 V. 1 : 2592 cttccaaggcatggtacagtaggactaatcactgtaactgatcctgattatggagacaat 2651 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 7 : 2577 cttccaaggcatggtacagtaggactaatcactgtaactgatcctgattatggagacaat 2636 V. 1 : 2652 tctgcagttacgctctccattttagatgagaatgatgacttcaccattgattcacaaact 2711 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 7 : 2637 tctgcagttacgctctccattttagatgagaatgatgacttcaccattgattcacaaact 2696 V. 1 : 2712 ggtgtcatccgaccaaatatttcatttgatagagaaaaacaagaatcttacactttctat 2771 Illlllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 7 : 2697 ggtgtcatccgaccaaatatttcatttgatagagaaaaacaagaatcttacactttctat 2756 V. 1 : 2772 gtaaaggctgaggatggtggtagagtatcacgttcttcaagtgccaaagtaaccataaat 2831 Illlllllllllllllllllllllllllllllllllllllllflllllllllllllllll V. 7 : 2757 gtaaaggctgaggatggtggtagagtatcacgttcttcaagtgccaaagtaaccataaat 2816 V. 1 : 2832 gtggttgatgtcaatgacaacaaaccagttttcattgtccctccttccaactgttcttat 2891 IIIlllllllllllllllllllllllllllllllllllllllllll IIIII IIIIIII V. 7 : 2817 gtggttgatgtcaatgacaacaaaccagttttcattgtccctccttacaactattcttat 2876 V. 1 : 2892 gaattggttctaccgtccactaatccaggcacagtggtctttcaggtaattgctgttgac 2951 Illlllllllllllllilllllllllllllllllllllllllllllllllllllllllll V. 7 : 2877 gaattggttctaccgtccactaatccaggcacagtggtctttcaggtaattgctgttgac 2936 V. 1 : 2952 aatgacactggcatgaatgcagaggttcgttacagcattgtaggaggaaacacaagagat 3011 Illlllllllllllllllllllllllllllllllllilllllllllllllllllllllll V. 7 : 2937 aatgacactggcatgaatgcagaggttcgttacagcattgtaggaggaaacacaagagat 2996 V. 1 : 3012 ctgtttgcaatcgaccaagaaacaggcaacataacattgatggagaaatgtgatgttaca 3071 IlllllllllllllllllllllllllllilllllllllllllUlllllllllllllllll V. 7 : 2997 ctgtttgcaatcgaccaagaaacaggcaacataacattgatggagaaatgtgatgttaca 3056 V. 1 : 3072 gaccttggtttacacagagtgttggtcaaagctaatgacttaggacagcctgattctctc 3131 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 7 : 3057 gaccttggtttacacagagtgttggtcaaagctaatgacttaggacagcctgattctctc 3116 V. 1 : 3132 ttcagtgttgtaattgtcaatctgttcgtgaatgagtcggtgaccaatgctacactgatt 3191 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII IIIIIIIIIIIIIIIIIIIII V. 7 : 3117 ttcagtgttgtaattgtcaatctgttcgtgaatgagtcagtgaccaatgctacactgatt 3176 V. 1 : 3192 aatgaactggtgcgcaaaagcactgaagcaccagtgaccccaaatactgagatagctgat 3251 IIIIIIIIIIIIIIIIIIIIII IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 7 : 3177 aatgaactggtgcgcaaaagcattgaagcaccagtgaccccaaatactgagatagctgat 3236 V. 1 : 3252 gtatcctcaccaactagtgactatgtcaagatcctggttgcagctgttgctggcaccata 3311 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 7 : 3237 gtatcctcaccaactagtgactatgtcaagatcctggttgcagctgttgctggcaccata 3296 V. 1 : 3312 actgtcgttgtagttattttcatcactgctgtagtaagatgtcgccaggcaccacacctt 3371 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 7 : 3297 actgtcgttgtagttattttcatcactgctgtagtaagatgtcgccaggcaccacacctt 3356 V. 1 : 3372 aaggctgctcagaaaaacaagcagaattctgaatgggctaccccaaacccagaaaacagg 3431 IIIIIIIIIIIIIIIIIII IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 7 : 3357 aaggctgctcagaaaaacatgcagaattctgaatgggctaccccaaacccagaaaacagg 3416 V. 1 : 3432 cagatgataatgatgaagaaaaagaaaaagaagaagaagcattcccctaagaacttgctg 3491 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII Illll V. 7 : 3417 cagatgataatgatgaagaaaaagaaaaagaagaagaagcattcccctaagaacctgctg 3476 V. 1 : 3492 cttaattttgtcactattgaagaaactaaggcagatgatgttgacagtgatggaaacaga 3551 IIIIII IIIIlllllllllllllllllllllllllllllllllllllllllllllllll V. 7 : 3477 cttaatgttgtcactattgaagaaactaaggcagatgatgttgacagtgatggaaacaga 3536 V. 1 : 3552 gtcacactagaccttcctattgatctagaagagcaaacaatgggaaagtacaattgggta 3611 Illllllllflllllllllllllllllllllllllllllllillllllllllllllllll V. 7 : 3537 gtcacactagaccttcctattgatctagaagagcaaacaatgggaaagtacaattgggta 3596 V. 1 : 3612 actacacctactactttcaagcccgacagccctgatttggcccgacactacaaatctgcc 3671 IIIIIIIIIIIIIIIIIIIIIII IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 7 : 3597 actacacctactactttcaagcctgacagccctgatttggcccgacactacaaatctgcc 3656 V. 1 : 3672 tctccacagcctgccttccaaattcagcctgaaactcccctgaattcgaagcaccacatc 3731 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII IIIIIIIIIIIII V. 7 : 3657 tctccacagcctgccttccaaattcagcctgaaactcccctgaatttgaagcaccacatc 3716 V. 1 : 3732 atccaagaactgcctctcgataacacctttgtggcctgtgactctatctccaagtgttcc 3791 Illllllllllllllllllllllilllllllllllllllllllllllllllll 111111 V. 7 : 3717 atccaagaactgcctctcgataacacctttgtggcctgtgactctatctccaattgttcc 3776 V. 1 : 3792 tcaagcagttcagatccctacagcgtttctgactgtggctatccagtgacgaccttcgag 3851 Illlllllllllllllllllllllllllllllllllllllllllllllll IIIIIIIII V. 7 : 3777 tcaagcagttcagatccctacagcgtttctgactgtggctatccagtgacaaccttcgag 3836 V. 1 : 3852 gtacctgtgtccgtacacaccagaccg 3878 IIIIIIIIIIIIIIIIIIIIIIIIII V. 7 : 3837 gtacctgtgtccgtacacaccagaccg 3863 Score = 1567 bits (815), Expect = O. OIdentities = 829/836 (99%) Strand = Plus Plus V. 1 : 3 ggtggtccagtacctccaaagatatggaatacactcctgaaatatcctgaaaactttttt 62 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII IIIIIII V. 7 : 1 ggtggtccagtacctccaaagatatggaatacactcctgaaatatcctgaaacctttttt 60 V. 1 : 63 ttttcagaatcctttaataagcagttatgtcaatctgaaagttgcttacttgtactttat 122 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 7 : 61 ttttcagaatcctttaataagcagttatgtcaa, tctgaaagttgcttacttgtactttat 120 V. 1 : 123 attaatagctattcttgtttttcttatccaaagaaaaatcctctaatccccttttcacat 182 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 7 : 121 attaatagctattcttgtttttcttatccaaagaaaaatcctctaatccccttttcacat 180 V. 1 : 183 gatagttgttaccatgtttaggcattagtcacatcaacccctctcctctcccaaacttct 242 IIIIIIIIIIIIIIIIIIIIIII IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 7 : 181 gatagttgttaccatgtttaggcgttagtcacatcaacccctctcctctcccaaacttct 240 V. 1 : 243 cttcttcaaatcaaactttattagtccctcctttataatgattccttgcctcgttttatc 302 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII IIIIIII V. 7 : 241 cttcttcaaatcaaactttattagtccctcctttataatgattccttgcctccttttatc 300 V. 1 : 303 cagatcaattttttttcactttgatgcccagagctgaagaaatggactactgtataaatt 362 IIIIlllllllllllllllllllllllllllllllllllllllllllll IIIIIIIIII V. 7 : 301 cagatcaattttttttcactttgatgcccagagctgaagaaatggactattgtataaatt 360 V. 1 : 363 attcattgccaagagaataattgcattttaaacccatattataacaaagaataatgatta 422 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII IIIIIIIIIIIIIIIIIIIIII V. 7 : 361 attcattgccaagagaataattgcattttaaacccatgttataacaaagaataatgatta 420 V. 1 : 423 tattttgtgatttgtaacaaataccctttattttcccttaactattgaattaaatatttt 482 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 7 : 421 tattttgtgatttgtaacaaataccctttattttcccttaactattgaattaaatatttt 480 V. 1 : 483 aattatttgtattctctttaactatcttggtatattaaagtattatcttttatatattta 542 Illilllllllllllllllllllllllllllllllllfllllllllllllllllllllll V. 7 : 481 aattatttgtattctctttaactatcttggtatattaaagtattatcttttatatattta 540 V. 1 : 543 tcaatggtggacacttttataggtactctgtgtcatttttgatactgtaggtatcttatt 602 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 7 : 541 tcaatggtggacacttttataggtactctgtgtcatttttgatactgtaggtatcttatt 600 V. 1 : 603 tcatttatctttattcttaatgtacgaattcataatatttgattcagaacaaatttatca 662 Illllllllllllllllllllllllllllllllllllllllllllllllll IIIIIIII V. 7 : 601 tcatttatctttattcttaatgtacgaattcataatatttgattcagaacagatttatca 660 V. 1 : 663 ctaattaacagagtgtcaattatgctaacatctcatttactgattttaatttaaaacagt 722 V. 7 : 661 ctaattaacagagtgtcaattatgctaacatctcatttactgattttaatttaaaacagt 720 V. 7. 661 ctaattaacagagtgtcaattatgctaacatctcatttactgattttaatttaaaacagt 720 V. 1 : 723 ttttgttaacatgcatgtttagggttggcttcttaataatttcttcttcctcttctctct 782 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 7 : 721 ttttgttaacatgcatgtttagggttggcttcttaataatttcttcttcctcttctctct 780 V. 1 : 783 ctcctcttcttttggtcagtgttgtgcgggttaatacaacaaactgtaacaagtgt 838 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII IIIlllll V. 7 : 781 ctcctcttcttttggtcagtgttgtgcgggttaatacaacaaactgtcacaagtgt 836 Table LIV(f). Peptide sequences of protein coded by 109P1D4 v. 7 (SEQ ID NO : 270) MFRVGFLIIS SSSSLSPLLL VSVVRVNTTN CHKCLLSGTY IFAVLLVCVV FHSGAQEKNY 60 TIREEIPENV LIGNLLKDLN LSLIPNKSLT TTMQFKLVYK TGDVPLIRIE EDTGEIFTTG 120 ARIDREKLCA GIPRDEHCFY EVEVAILPDE IFRLVKIRFL IEDINDNAPL FPATVINISI 180 PENSAINSKY TLPAAVDPDV GINGVQNYEL IKSQNIFGLD VIETPEGDKM PQLIVQKELD 240 REEKDTYVMK VKVEDGGFPQ RSSTAILQVS VTDTNDNHPV FKETEIEVSI PENAPVGTSV 300 TQLHATDADI GENAKIHFSF SNLVSNIARR LFHLNATTGL ITIKEPLDRE ETPNHKLLVL 360 ASDGGLMPAR AMVLVNVTDV NDNVPSIDIR YIVNPVNDTV VLSENIPLNT KIALITVTDK 420 DADHNGRVTC FTDHEIPFRL RPVFSNQFLL ENAAYLDYES TKEYAIKLLA ADAGKPPLNQ 480 SAMLFIKVKD ENDNAPVFTQ SFVTVSIPEN NSPGIQLMKV SATDADSGPN AEINYLLGPD 540 APPEFSLDRR TGMLTWKKL DREKEDKYLF TILAKDNGVP PLTSNVTVFV SIIDQNDNSP 600 VFTHNEYKFY VPENLPRHGT VGLITVTDPD YGDNSAVTLS ILDENDDFTI DSQTGVIRPN 660 ISFDREKQES YTFYVKAEDG GRVSRSSSAK VTINVVDVND NKPVFIVPPY NYSYELVLPS 720 TNPGTWFQV IAVDNDTGMN AEVRYSIVGG NTRDLFAIDQ ETGNITLMEK CDVTDLGLHR 780 VLVKANDLGQ PDSLFSWIV NLFVNESVTN ATLINELVRK SIEAPVTPNT EIADVSSPTS 840 DYVKILVAAV AGTITWWI FITAWRCRQ APHLKAAQKN MQNSEWATPN PENRQMIMMK 900 KKKKKKKHSP KNLLLNWTI EETKADDVDS DGNRVTLDLP IDLEEQTMGK YNWVTTPTTF 960 KPDSPDLARH YKSASPQPAF QIQPETPLNL KHHIIQELPL DNTFVACDSI SNCSSSSSDP 1020 YSVSDCGYPV TTFEVPVSVH TRPTDSRT 1048 Table LV(f). Amino acid sequence alignment of 109P1D4 v.1 (SEQ ID NO : 271) and 109P1D4 v.7 (SEQ ID NO : 272) Score = 1961 bits (5081), Expect = O. Oldentities = 992/1009 (98%), Positives = 995/1009 (98%) V. 1 : 3 LLSGTYIFAVLLACWFHSGAQEKNYTIREEMPENVLIGDLLKDLNLSLIPNKSLTTAMQ 62 LLSGTYIFAVLL CWFHSGAQEKNYTIREE+PENVLIG+LLKDLNLSLIPNKSLTT MQ V. 7 : 35 LLSGTYIFAVLLVCWFHSGAQEKNYTIREEIPENVLIGNLLKDLNLSLIPNKSLTTTMQ 94 V. 1 : 63 FKLVYKTGDVPLIRIEEDTGEIFTTGARIDREKLCAGIPRDEHCFYEVEVAILPDEIFRL 122 FKLVYKTGDVPLIRIEEDTGEIFTTGARIDREKLCAGIPRDEHCFYEVEVAILPDEIFRL V. 7 : 95 FKLVYKTGDVPLIRIEEDTGEIFTTGARIDREKLCAGIPRDEHCFYEVEVAILPDEIFRL 154 V. 1 : 123 VKIRFLIEDINDNAPLFPATVINISIPENSAINSKYTLPAAVDPDVGINGVQNYELIKSQ 182 VKIRFLIEDINDNAPLFPATVINISIPENSAINSKYTLPAAVDPDVGINGVQNYELIKSQ V. 7 : 155 VKIRFLIEDINDNAPLFPATVINISIPENSAINSKYTLPAAVDPDVGINGVQNYELIKSQ 214 V. 1 : 183 NIFGLDVIETPEGDKMPQLIVQKELDREEKDTYVMKVKVEDGGFPQRSSTAILQVSVTDT 242 NIFGLDVIETPEGDKMPQLIVQKELDREEKDTYVMKVKVEDGGFPQRSSTAILQVSVTDT V. 7 : 215 NIFGLDVIETPEGDKMPQLIVQKELDREEKDTYVMKVKVEDGGFPQRSSTAILQVSVTDT 274 V. 1 : 243 NDNHPVFKETEIEVSIPENAPVGTSVTQLHATDADIGENAKIHFSFSNLVSNIARRLFHL 302 NDNHPVFKETEIEVSIPENAPVGTSVTQLHATDADIGENAKIHFSFSNLVSNIARRLFHL V. 7 : 275 NDNHPVFKETEIEVSIPENAPVGTSVTQLHATDADIGENAKIHFSFSNLVSNIARRLFHL 334 V. 1 : 303 NATTGLITIKEPLDREETPNHKLLVLASDGGLMPARAMVLVNVTDVNDNVPSIDIRYIVN 362 NATTGLITIKEPLDREETPNHKLLVLASDGGLMPARAMVLVNVTDVNDNVPSIDIRYIVN V. 7 : 335 NATTGLITIKEPLDREETPNHKLLVLASDGGLMPARAMVLVNVTDVNDNVPSIDIRYIVN 394 V. 1 : 363 PVNDTVVLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLETAA 422 PVNDTVVLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLE AA V. 7 : 395 PVNDTWLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLENAA 454 V. 1 : 423 YLDYESTKEYAIKLLAADAGKPPLNQSAMLFIKVKDENDNAPVFTQSFVTVSIPENNSPG 482 YLDYESTKEYAIKLLAADAGKPPLNQSAMLFIKVKDENDNAPVFTQSFVTVSIPENNSPG V. 7 : 455 YLDYESTKEYAIKLLAADAGKPPLNQSAMLFIKVKDENDNAPVFTQSFVTVSIPENNSPG 514 V. 1 : 483 IQLTKVSAMDADSGPNAKINYLLGPDAPPEFSLDCRTGMLTWKKLDREKEDKYLFTILA 542 IQL KVSA DADSGPNA+INYLLGPDAPPEFSLD RTGMLTWKKLDREKEDKYLFTILA V. 7 : 515 IQLMKVSATDADSGPNAEINYLLGPDAPPEFSLDRRTGMLTWKKLDREKEDKYLFTILA 574 V. 1 : 543 KDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEYNFYVPENLPRHGTVGLITVTDPDYGDN 602 KDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEY FYVPENLPRHGTVGLITVTDPDYGDN V. 7 : 575 KDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEYKFYVPENLPRHGTVGLITVTDPDYGDN 634 V. 1 : 603 SAVTLSILDENDDFTIDSQTGVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVTIN 662 SAVTLSILDENDDFTIDSQTGVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVTIN V. 7 : 635 SAVTLSILDENDDFTIDSQTGVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVTIN 694 V. 1 : 663 WDVNDNKPVFIVPPSNCSYELVLPSTNPGTVVFQVIAVDNDTGMNAEVRYSIVGGNTRD 722 WDVNDNKPVFIVPP N SYELVLPSTNPGTVVFQVIAVDNDTGMNAEVRYSIVGGNTRD V. 7 : 695 WDVNDNKPVFIVPPYNYSYELVLPSTNPGTWFQVIAVDNDTGMNAEVRYSIVGGNTRD 754 V. 1 : 723 LFAIDQETGNITLMEKCDVTDLGLHRVLVKANDLGQPDSLFSWIVNLFVNESVTNATLI 782 LFAIDQETGNITLMEKCDVTDLGLHRVLVKANDLGQPDSLFSWIVNLFVNESVTNATLI V. 7 : 755 LFAIDQETGNITLMEKCDVTDLGLHRVLVKANDLGQPDSLFSWIVNLFVNESVTNATLI 814 V. 1 : 783 NELVRKSTEAPVTPNTEIADVSSPTSDYVKILVAAVAGTITWWIFITAWRCRQAPHL 842 NELVRKS EAPVTPNTEIADVSSPTSDYVKILVAAVAGTITVWVIFITAWRCRQAPHL V. 7 : 815 NELVRKSIEAPVTPNTEIADVSSPTSDYVKILVAAVAGTITVWVIFITAVVRCRQAPHL 874 V. 1 : 843 KAAQKNKQNSEWATPNPENRQMIMMKKKKKKKKHSPKNLLLNFVTIEETKADDVDSDGNR 902 KAAQKN QNSEWATPNPENRQMIMMKKKKKKKKHSPKNLLLN VTIEETKADDVDSDGNR V. 7 : 875 KAAQKNMQNSEWATPNPENRQMIMMKKKKKKKKHSPKNLLLNWTIEETKADDVDSDGNR 934 V. 1 : 903 VTLDLPIDLEEQTMGKYNWVTTPTTFKPDSPDLARHYKSASPQPAFQIQPETPLNSKHHI 962 VTLDLPIDLEEQTMGKYNWVTTPTTFKPDSPDLARHYKSASPQPAFQIQPETPLN KHHI V. 7 : 935 VTLDLPIDLEEQTMGKYNWVTTPTTFKPDSPDLARHYKSASPQPAFQIQPETPLNLKHHI 994 V. 1 : 963 IQELPLDNTFVACDSISKCSSSSSDPYSVSDCGYPVTTFEVPVSVHTRP 1011 IQELPLDNTFVACDSIS CSSSSSDPYSVSDCGYPVTTFEVPVSVHTRP V. 7 : 995 IQELPLDNTFVACDSISNCSSSSSDPYSVSDCGYPVTTFEVPVSVHTRP 1043 Table LII (g). Nucleotide sequence of transcript variant 109P1D4 v.8 (SEQ ID NO : 273) ggtggtccag tacctccaaa gatatggaat acactcctga aatatcctga aacctttttt 60 ttttcagaat cctttaataa gcagttatgt caatctgaaa gttgcttact tgtactttat 120 attaatagct attcttgttt ttcttatcca aagaaaaatc ctctaatccc cttttcacat 180 gatagttgtt accatgttta ggcgttagtc acatcaaccc ctctcctctc ccaaacttct 240 cttcttcaaa tcaaacttta ttagtccctc ctttataatg attccttgcc tccttttatc 300 cagatcaatt ttttttcact ttgatgccca gagctgaaga aatggactat tgtataaatt 360 attcattgcc aagagaataa ttgcatttta aacccatgtt ataacaaaga ataatgatta 420 tattttgtga tttgtaacaa atacccttta ttttccctta actattgaat taaatatttt 480 aattatttgt attctcttta actatcttgg tatattaaag tattatcttt tatatattta 540 tcaatggtgg acacttttat aggtactctg tgtcattttt gatactgtag gtatcttatt 600 tcatttatct ttattcttaa tgtacgaatt cataatattt gattcagaac agatttatca 660 ctaattaaca gagtgtcaat tatgctaaca tctcatttac tgattttaat ttaaaacagt 720 ttttgttaac atgcatgttt agggttggct tcttaataat ttcttcttcc tcttctctct 780 ctcctcttct tttggtcagt gttgtgcggg ttaatacaac aaactgtcac aagtgtttgt 840 tgtccgggac gtacattttc gcggtcctgc tagtatgcgt ggtgttccac tctggcgccc 900 aggagaaaaa ctacaccatc cgagaagaaa ttccagaaaa cgtcctgata ggcaacttgt 960 tgaaagacct taacttgtcg ctgattccaa acaagtcctt gacaactact atgcagttca 1020 agctagtgta caagaccgga gatgtgccac tgattcgaat tgaagaggat actggtgaga 1080 tcttcactac cggcgctcgc attgatcgtg agaaattatg tgctggtatc ccaagggatg 1140 agcattgctt ttatgaagtg gaggttgcca ttttgccgga tgaaatattt agactggtta 1200 agatacgttt tctgatagaa gatataaatg ataatgcacc attgttccca gcaacagtta 1260 tcaacatatc aattccagag aactcggcta taaactctaa atatactctc ccagcggctg 1320 ttgatcctga cgtaggcata aacggagttc aaaactacga actaattaag agtcaaaaca 1380 tttttggcct cgatgtcatt gaaacaccag aaggagacaa gatgccacaa ctgattgttc 1440 aaaaggagtt agatagggaa gagaaggata cctatgtgat gaaagtaaag gttgaagatg 1500 gtggctttcc tcaaagatcc agtactgcta ttttgcaagt aagtgttact gatacaaatg 1560 acaaccaccc agtctttaag gagacagaga ttgaagtcag tataccagaa aatgctcctg 1620 taggcacttc agtgacacag ctccatgcca cagatgctga cataggtgaa aatgccaaga 1680 tccacttctc tttcagcaat ctagtctcca acattgccag gagattattt cacctcaatg 1740 ccaccactgg acttatcaca atcaaagaac cactggatag ggaagaaaca ccaaaccaca 1800 agttactggt tttggcaagt gatggtggat tgatgccagc aagagcaatg gtgctggtaa 1860 atgttacaga tgtcaatgat aatgtcccat ccattgacat aagatacatc gtcaatcctg 1920 tcaatgacac agttgttctt tcagaaaata ttccactcaa caccaaaatt gctctcataa 1980 ctgtgacgga taaggatgcg gaccataatg gcagggtgac atgcttcaca gatcatgaaa 2040 ttcctttcag attaaggcca gtattcagta atcagttcct cctggagaat gcagcatatc 2100 ttgactatga gtccacaaaa gaatatgcca ttaaattact ggctgcagat gctggcaaac 2160 ctcctttgaa tcagtcagca atgctcttca tcaaagtgaa agatgaaaat gacaatgctc 2220 cagttttcac ccagtctttc gtaactgttt ctattcctga gaataactct cctggcatcc 2280 agttgatgaa agtaagtgca acggatgcag acagtgggcc taatgctgag atcaattacc 2340 tgctaggccc tgatgctcca cctgaattca gcctggatcg tcgtacaggc atgctgactg 2400 tagtgaagaa actagataga gaaaaagagg ataaatattt attcacaatt ctggcaaaag 2460 ataatggggt accaccctta accagcaatg tcacagtctt tgtaagcatt attgatcaga 2520 atgacaatag cccagttttc actcacaatg aatacaaatt ctatgtccca gaaaaccttc 2580 caaggcatgg tacagtagga ctaatcactg taactgatcc tgattatgga gacaattctg 2640 cagttacgct ctccatttta gatgagaatg atgacttcac cattgattca caaactggtg 2700 tcatccgacc aaatatttca tttgatagag aaaaacaaga atcttacact ttctatgtaa 2760 aggctgagga tggtggtaga gtatcacgtt cttcaagtgc caaagtaacc ataaatgtgg 2820 ttgatgtcaa tgacaacaaa ccagttttca ttgtccctcc ttacaactat tcttatgaat 2880 tggttctacc gtccactaat ccaggcacag tggtctttca ggtaattgct gttgacaatg 2940 acactggcat gaatgcagag gttcgttaca gcattgtagg aggaaacaca agagatctgt 3000 ttgcaatcga ccaagaaaca ggcaacataa cattgatgga gaaatgtgat gttacagacc 3060 ttggtttaca cagagtgttg gtcaaagcta atgacttagg acagcctgat tctctcttca 3120 gtgttgtaat tgtcaatctg ttcgtgaatg agtcagtgac caatgctaca ctgattaatg 3180 aactggtgcg caaaagcatt gaagcaccag tgaccccaaa tactgagata gctgatgtat 3240 cctcaccaac tagtgactat gtcaagatcc tggttgcagc tgttgctggc accataactg 3300 tcgttgtagt tattttcatc actgctgtag taagatgtcg ccaggcacca caccttaagg 3360 ctgctcagaa aaacatgcag aattctgaat gggctacccc aaacccagaa aacaggcaga 3420 tgataatgat gaagaaaaag aaaaagaaga agaagcattc ccctaagaac ctgctgctta 3480 atgttgtcac tattgaagaa actaaggcag atgatgttga cagtgatgga aacagagtca 3540 cactagacct tcctattgat ctagaagagc aaacaatggg aaagtacaat tgggtaacta 3600 cacctactac tttcaagcct gacagccctg atttggcccg acactacaaa tctgcctctc 3660 cacagcctgc cttccaaatt cagcctgaaa ctcccctgaa tttgaagcac cacatcatcc 3720 aagaactgcc tctcgataac acctttgtgg cctgtgactc tatctccaat tgttcctcaa 3780 gcagttcaga tccctacagc gtttctgact gtggctatcc agtgacaacc ttcgaggtac 3840 ctgtgtccgt acacaccaga ccgtcccagc ggcgtgtcac atttcacctg ccagaaggct 3900 ctcaggaaag cagcagtgat ggtggactgg gagaccatga tgcaggcagc cttaccagca 3960 catcccatgg cctgcccctt ggctatcctc aggaggagta ctttgatcgt gctacaccca 4020 gcaatcgcac tgaaggggat ggcaactccg atcctgaatc tactttcata cctggactaa 4080 agaaagaaat aactgttcaa ccaactgtgg aagaggcctc tgacaactgc actcaagaat 4140 gtctcatcta tggccattct gatgcctgct ggatgccggc atctctggat cattccagct 4200 cttcacaagc acaggcctct gctctatgcc acagcccacc actgtcacag gcctctactc 4260 agcaccacag cccaccagtg acacagacca ttgttctctg ccacagccct ccagtgacac 4320 agaccatcgc attgtgccac agcccaccac cgatacaggt gtctgctctc caccacagtc 4380 ctcctctagt gcagggtact gcacttcacc acagcccacc atcagcacag gcctcagccc 4440 tctgctacag ccctccttta gcacaggctg ctgcaatcag ccacagctct tctctgccac 4500 aggttattgc cctccatcgt agtcaggccc aatcatcagt cagtttgcag caaggttggg 4560 tgcaaggtgc taatggacta tgctctgttg atcagggagt gcaaggtagt gcaacatctc 4620 agttttacac catgtctgaa agacttcatc ccagtgatga ttcaattaaa gtcattcctt 4680 tgacaacctt cgctccacgc caacaggcca gaccgtccag aggtgattcc cccattatgg 4740 aaacacatcc cttgtaaagc taaaatagtt acttcaaatt ttcagaaaag atgtatatag 4800 tcaaaattta agatacaatt ccaatgagta ttctgattat cagatttgta aataactatg 4860 taaatagaaa cagataccag aataaatcta cagctagacc cttagtcaat agttaaccaa 4920 aaaattgcaa tttgtttaat tcagaatgtg tatttaaaaa gaaaaggaat ttaacaattt 4980 gcatcccctt gtacagtaag gcttatcatg acagagcgta ctatttctga tgtacagtat 5040 tttttgttgt ttttatcatc atgtgcaata ttactgattt gtttccatgc tgattgtgtg 5100 gaaccagtat gtagcaaatg gaaagcctag aaatatctta ttttctaagt ttacctttag 5160 tttacctaaa cttttgttca gataatgtta aaaggtatac gtactctagc cttttttggg 5220 gctttctttt tgatttttgt ttgtggtttt cagttttttt gttgttgtta gtgagtctcc 5280 cttcaaaata cacagtaggt agtgtaaata ctgcttgttt gtgtctctct gctgtcatgt 5340 tttctacctt attccaatac tatattgttg ataaaatttg tatatacatt ttcaataaag 5400 aatatgtata aactgtacag atctagatct acaacctatt tctctactct ttagtagagt 5460 tcgagacaca gaagtgcaat aactgcccta attaagcaac tatttgttaa aaagggcccc 5520 tttttacttt aatagtttag tgtaaagtac atcagaaata aaactgtatc tgacatttta 5580 agcctgtagt ccattattac ttgggtcttt acttctggga atttgtatgt aacagcctag 5640 aaaattaaaa ggaggtggat gcatccaaag cacgagtcac ttaaaatatc gacggtaaac 5700 tactattttg tagagaaact caggaagatt taaatgttga tttgacagct caataggctg 5760 ttaccaaagg gtgttcagta aaaataacaa atacatgtaa ctgtagataa aaccacatac 5820 taaatctata agactaaggg atttttgtta ttctagctca acttactgaa gaaaaccact 5880 aataacaaca agaatatcag gaaggaactt ttcaagaaat gtaattataa atctacatca 5940 aacagaattt taaggaaaaa tgcagaggga gaaataaggc acatgactgc ttcttgcagt 6000 caagaagaaa taccaataac acacacagaa caaaaaccat caaaatctca tatatgaaat 6060 aaaatatatt cttctaagca aagaaacagt actattcata gaaaacatta gttttctcct 6120 gttgtctgtt atttccttct tttatcctct taactggcca ttatcttgta tgtgcacatt 6180 ttataaatgt acagaaacat caccaacttg attttcttcc atagcaaaac tgagaaaata 6240 ccttgtttca gtataacact aaaccaagag acaattgatg tttaatgggg gcggttgggg 6300 ttggggggga gtcaatatct cctattgatt aacttagaca tagattttgt aatgtataac 6360 ttgatattta atttatgatt aaactgtaat tttgtaacat aaactgtggt aattgcataa 6420 tttcattggt gaggatttcc tttgaatatt gagaaagttt cttttcatgt gcccagcagg 6480 ttaagtagcg ttttcagaat atacattatt cccatccatt gtaaagttcc ttaagtcata 6540 tttgactggg cgtgcagaat aacttcttaa ctattaacta tcagagtttg attaataaaa 6600 ttaattaatt ttttttctcc ttcgtgttgt taatgttcca agggatttgg agcatactgg 6660 ttttccaggt gcatgtgaat cccgaaggac tgatgatatt tgaatgttta ttaaattatt 6720 atcacacaaa tgtgttgata ttgtggctat tgttgatgtt gaaaattgta aacttgggga 6780 agattaagaa aagaaccaat agtgacaaaa atcagtgctt ccagtagatt ttagaacatt 6840 ctttgcctca aaaaacctgc aaagatgatg tgagattttt tcttgtgttt taattatttt 6900 cacattttct ctctgcaaac ctttagtttt ctgatgatct acacacacac atacacacac 6960 acacacacac acgtgcacac acacacattt aaaggatata aaaagaagag gttgaaagat 7020 tattaaataa cttatcaggc atctcaatgg ttactatcta tgttagtgaa aatcaaatag 7080 gactcaaagt tggatatttg ggatttttct tctgacagta taatttattg agttactagg 7140 gaggttctta aatcctcata tctggaaact tgtgaagttt tgacaccttt cctatagata 7200 taggaatgaa ccaatacgct tttattaccc tttctaactc tgattttata atcagactta 7260 gattgtgttt agaatattaa atgactgggc accctcttct tggtttttac cagagaggct 7320 ttgaatggaa gcaggctgag agtagccaaa gaggcaaggg gtattagccc agttattctc 7380 ccctatgcct tctcttccta agcgtccact aggtctggcc ttggaaatct gttacttcta 7440 cggcttcaga tctgatgata tctttttcat cacattacaa gttatttctt tgactgaata 7500 gacagtggta taggttgaca cagcacacaa gtggctattg tgatgtatga tgtatgtagt 7560 cccacaactg caaaacgtct tactgaagca acaatcgaaa aatggttctg ttttaaaaag 7620 gattttgttt gatttgaaat taaaacttca aactgaatga cttatatgag aataatatgt 7680 tcaatcaaag tagttattct attttgtgtc catattccat tagattgtga ttattaattt 7740 tctagctatg gtattactat atcacacttg tgagtatgta ttcaaatact aagtatctta 7800 tatgctacgt gcatacacat tcttttctta aactttacct gtgttttaac taatattgtg 7860 tcagtgtatt aaaaattagc ttttacatat gatatctaca atgtaataaa tttagagagt 7920 aattttgtgt attcttattt acttaacatt ttacttttaa ttatgtaaat ttggttagaa 7980 aataataata aatggttagt gctattgtgt aatggtagca gttacaaaga gcctctgcct 8040 tcccaaacta atatttatca cacatggtca ttaaatggga aaaaaataga ctaaacaaat 8100 cacaaattgt tcagttctta aaatgtaatt atgtcacaca cacaaaaaaa tccttttcaa 8160 tcctgagaaa attaaaggtg ttttactcac atggatattt caacattagt tttttttgtt 8220 tgtttctttt tcatggtatt actgaaggtg tgtatactcc ctaatacaca tttatgaaaa 8280 tctacttgtt tagactttta tttatactct tctgatttat attttttatt ataattatta 8340 tttcttatct tcttttatat tttttggaaa ccaaatttat agttagttta ggtaaacttt 8400 ttattatgac cattagaaac tattttgaat gtttccaact ggctcaattg gctgggaaaa 8460 catgggaaca agagaagctg aaatatattt ctgcaagaac ctttctatat tatgtgccaa 8520 ttaccacacc agatcaattt tatgcagagg ccttaaaata ttctttcaca gtagctttct 8580 tacactaacc gtcatgtgct tttagtaaat atgattttta aaagcagttc aagttgacaa 8640 cagcagaaac agtaacaaaa aaatctgctc agaaaaatgt atgtgcacaa ataaaaaaaa 8700 ttaatggcaa ttgtttagtg actgtaagtg atacttttta aagagtaaac tgtgtgaaat 8760 ttatactatc cctgcttaaa atattaagat ttttatgaaa tatgtattta tgtttgtatt 8820 gtgggaagat tcctcctctg tgatatcata cagcatctga aagtgaacag tatcccaaag 8880 cagttccaag catgctttgg aagtaagaag gttgactatt gtatggccaa ggatggcagt 8940 atgtaatcca gaagcaaact tgtattaatt gttctatttc aggttctgta ttgcatgttt 9000 tcttattaat atatattaat aaaagttatg agaaat 9036 Table Lull (g). Nucleotide sequence alignment of 109P1D4 v. 1 (SEQ ID NO : 274) and 109P1D4 v. 8 (SEQ ID NO : 275) Score = 5664 bits (2946), Expect = O. Oldentities = 3000/3027 (99%) Strand = Plus/Plus V. 1 : 852 ttgttgtccgggacgtacattttcgcggtcctgctagcatgcgtggtgttccactctggc 911 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII IIIIIIIIIIIIIIIIIIIIII V. 8 : 837 ttgttgtccgggacgtacattttcgcggtcctgctagtatgcgtggtgttccactctggc 896 V. 1 : 912 gcccaggagaaaaactacaccatccgagaagaaatgccagaaaacgtcctgataggcgac 971 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII IIIIIIIIIIIIIIIIIIIII II V. 8 : 897 gcccaggagaaaaactacaccatccgagaagaaattccagaaaacgtcctgataggcaac 956 V. 1 : 972 ttgttgaaagaccttaacttgtcgctgattccaaacaagtccttgacaactgctatgcag 1031 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII IIIIIIII V. 8 : 957 ttgttgaaagaccttaacttgtcgctgattccaaacaagtccttgacaactactatgcag 1016 V. 1 : 1032 ttcaagctagtgtacaagaccggagatgtgccactgattcgaattgaagaggatactggt 1091 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 8 : 1017 ttcaagctagtgtacaagaccggagatgtgccactgattcgaattgaagaggatactggt 1076 V. 1 : 1092 gagatcttcactactggcgctcgcattgatcgtgagaaattatgtgctggtatcccaagg 1151 IIIIIIIIIIIIII Illllllllllllllllllllllilllllllllllllllllllll V. 8 : 1077 gagatcttcactaccggcgctcgcattgatcgtgagaaattatgtgctggtatcccaagg 1136 V. 1 : 1152 gatgagcattgcttttatgaagtggaggttgccattttgccggatgaaatatttagactg 1211 Illlllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 8 : 1137 gatgagcattgcttttatgaagtggaggttgccattttgccggatgaaatatttagactg 1196 V. 1 : 1212 gttaagatacgttttctgatagaagatataaatgataatgcaccattgttcccagcaaca 1271 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 8 1197 gttaagatacgttttctgatagaagatataaatgataatgcaccattgttcccagcaaca 1256 V. 1 : 1272 gttatcaacatatcaattccagagaactcggctataaactctaaatatactctcccagcg 1331 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIilllllllllllllllllllll V. 8 1257 gttatcaacatatcaattccagagaactcggctataaactctaaatatactctcccagcg 1316 V. 1 : 1332 gctgttgatcctgacgtaggaataaacggagttcaaaactacgaactaattaagagtcaa 1391 IIIIIIIIIIIIIIIIIIII IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 8 : 1317 gctgttgatcctgacgtaggcataaacggagttcaaaactacgaactaattaagagtcaa 1376 V. 1 : 1392 aacatttttggcctcgatgtcattgaaacaccagaaggagacaagatgccacaactgatt 1451 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 8 : 1377 aacatttttggcctcgatgtcattgaaacaccagaaggagacaagatgccacaactgatt 1436 V. 1 : 1452 gttcaaaaggagttagatagggaagagaaggatacctacgtgatgaaagtaaaggttgaa 1511 llllllllllllllllllllllllllllllllllllll IIIIIIIIIIIIIIIIIIIII V. 8 : 1437 gttcaaaaggagttagatagggaagagaaggatacctatgtgatgaaagtaaaggttgaa 1496 V. 1 : 1512 gatggtggctttcctcaaagatccagtactgctattttgcaagtgagtgttactgataca 1571 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII IIIIIIIIIIIIIII V. 8 : 1497 gatggtggctttcctcaaagatccagtactgctattttgcaagtaagtgttactgataca 1556 V. 1 : 1572 aatgacaaccacccagtctttaaggagacagagattgaagtcagtataccagaaaatgct 1631 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 8 : 1557 aatgacaaccacccagtctttaaggagacagagattgaagtcagtataccagaaaatgct 1616 V. 1 : 1632 cctgtaggcacttcagtgacacagctccatgccacagatgctgacataggtgaaaatgcc 1691 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIilllllllllllllllllllllllll V. 8 : 1617 cctgtaggcacttcagtgacacagctccatgccacagatgctgacataggtgaaaatgcc 1676 V. 1 : 1692 aagatccacttctctttcagcaatctagtctccaacattgccaggagattatttcacctc 1751 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 8 : 1677 aagatccacttctctttcagcaatctagtctccaacattgccaggagattatttcacctc 1736 V. 1 : 1752 aatgccaccactggacttatcacaatcaaagaaccactggatagggaagaaacaccaaac 1811 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 8 : 1737 aatgccaccactggacttatcacaatcaaagaaccactggatagggaagaaacaccaaac 1796 V. 1 : 1812 cacaagttactggttttggcaagtgatggtggattgatgccagcaagagcaatggtgctg 1871 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 8 : 1797 cacaagttactggttttggcaagtgatggtggattgatgccagcaagagcaatggtgctg 1856 V. 1 : 1872 gtaaatgttacagatgtcaatgataatgtcccatccattgacataagatacatcgtcaat 1931 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 8 : 1857 gtaaatgttacagatgtcaatgataatgtcccatccattgacataagatacatcgtcaat 1916 V. 1 : 1932 cctgtcaatgacacagttgttctttcagaaaatattccactcaacaccaaaattgctctc 1991 m m m m m m m m m m m m m n m m m m m m n V. 8. 1917 cctgtcaatgacacagttgttctttcagaaaatattccactcaacaccaaaattgctctc 1976 V. 8 : 1917 cCtgtcaatgacacagttgttctttcagaaaatattccactcaacaccaaaattgCtCtc 1976 V. 1 1992 ataactgtgacggataaggatgcggaccataatggcagggtgacatgcttcacagatcat 2051 Illlllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 8 1977 ataactgtgacggataaggatgcggaccataatggcagggtgacatgcttcacagatcat 2036 V. 1 : 2052 gaaatccctttcagattaaggccagtattcagtaatcagttcctcctggagactgcagca 2111 IIIII Illllllllllllllllllllllllllllllllllllillllllll IIIIIII V. 8 : 2037 gaaattcctttcagattaaggccagtattcagtaatcagttcctcctggagaatgcagca 2096 V. 1 : 2112 tatcttgactatgagtccacaaaagaatatgccattaaattactggctgcagatgctggc 2171 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 8 : 2097 tatcttgactatgagtccacaaaagaatatgccattaaattactggctgcagatgctggc 2156 V. 1 : 2172 aaacctcctttgaatcagtcagcaatgctcttcatcaaagtgaaagatgaaaatgacaat 2231 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIillllllll V. 8 : 2157 aaacCtcCtttgaatcagtcagcaatgctcttcatcaaagtgaaagatgaaaatgacaat 2216 V. 1 : 2232 gctccagttttcacccagtctttcgtaactgtttctattcctgagaataactctcctggc 2291 IIIIllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 8 : 2217 gctccagttttcacccagtctttcgtaactgtttctattcctgagaataactctcctggc 2276 V. 1 : 2292 atccagttgacgaaagtaagtgcaatggatgcagacagtgggcctaatgctaagatcaat 2351 IIIIllllll IIIIIIIIIIIIII IIIIIIIIIIIIIIIIIIIIIIIII llllllll V. 8 : 2277 atccagttgatgaaagtaagtgcaacggatgcagacagtgggcctaatgctgagatcaat 2336 V. 1 : 2352 tacctgctaggccctgatgctccacctgaattcagcctggattgtcgtacaggcatgctg 2411 111111111111|11111111111111111111111111111 11111111111111111 V. 8 : 2337 tacctgctaggccctgatgctccacctgaattcagcctggatcgtcgtacaggcatgctg 2396 V. 1 : 2412 actgtagtgaagaaactagatagagaaaaagaggataaatatttattcacaattctggca 2471 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIlllllllllllllllllllllllllllll V. 8. 2397 actgtagtgaagaaactagatagagaaaaagaggataaatatttattcacaattctggca 2456 V. 1 : 2472 aaagataacggggtaccacccttaaccagcaatgtcacagtctttgtaagcattattgat 2531 IIIIIIII IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 8 : 2457 aaagataatggggtaccacccttaaccagcaatgtcacagtctttgtaagcattattgat 2516 V. 1 : 2532 cagaatgacaatagcccagttttcactcacaatgaatacaacttctatgtcccagaaaac 2591 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII IIIlllllllllllllll V. 8 : 2517 cagaatgacaatagcccagttttcactcacaatgaatacaaattctatgtcccagaaaac 2576 V. 1 : 2592 cttccaaggcatggtacagtaggactaatcactgtaactgatcctgattatggagacaat 2651 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 8 : 2577 cttccaaggcatggtacagtaggactaatcactgtaactgatcctgattatggagacaat 2636 V. 1 : 2652 tctgcagttacgctctccattttagatgagaatgatgacttcaccattgattcacaaact 2711 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 8 : 2637 tctgcagttacgctctccattttagatgagaatgatgacttcaccattgattcacaaact 2696 V. 1 : 2712 ggtgtcatccgaccaaatatttcatttgatagagaaaaacaagaatcttacactttctat 2771 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 8 : 2697 ggtgtcatccgaccaaatatttcatttgatagagaaaaacaagaatcttacactttctat 2756 V. 1 : 2772 gtaaaggctgaggatggtggtagagtatcacgttcttcaagtgccaaagtaaccataaat 2831 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 8 : 2757 gtaaaggctgaggatggtggtagagtatcacgttcttcaagtgccaaagtaaccataaat 2816 V. 1 : 2832 gtggttgatgtcaatgacaacaaaccagttttcattgtccctccttccaactgttcttat 2891 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII IIIII IIIIIII V. 8 : 2817 gtggttgatgtcaatgacaacaaaccagttttcattgtccctccttacaactattcttat 2876 V. 1 : 2892 gaattggttctaccgtccactaatccaggcacagtggtctttcaggtaattgctgttgac 2951 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 8 : 2877 gaattggttctaccgtccactaatccaggcacagtggtctttcaggtaattgctgttgac 2936 V. 1 : 2952 aatgacactggcatgaatgcagaggttcgttacagcattgtaggaggaaacacaagagat 3011 llllllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 8 : 2937 aatgacactggcatgaatgcagaggttcgttacagcattgtaggaggaaacacaagagat 2996 V. 1 : 3012 ctgtttgcaatcgaccaagaaacaggcaacataacattgatggagaaatgtgatgttaca 3071 llllllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 8 : 2997 ctgtttgcaatcgaccaagaaacaggcaacataacattgatggagaaatgtgatgttaca 3056 V. 1 : 3072 gaccttggtttacacagagtgttggtcaaagctaatgacttaggacagcctgattctctc 3131 Illlllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 8 : 3057 gaccttggtttacacagagtgttggtcaaagctaatgacttaggacagcctgattctctc 3116 V. 1 : 3132 ttcagtgttgtaattgtcaatctgttcgtgaatgagtcggtgaccaatgctacactgatt 3191 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII Illllllllllllllllllll V. 8 : 3117 ttcagtgttgtaattgtcaatctgttcgtgaatgagtcagtgaccaatgctacactgatt 3176 V. 1 : 3192 aatgaactggtgcgcaaaagcactgaagcaccagtgaccccaaatactgagatagctgat 3251 IIIIllllllllllllllllll IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 8 : 3177 aatgaactggtgcgcaaaagcattgaagcaccagtgaccccaaatactgagatagctgat 3236 V. 1 : 3252 gtatcctcaccaactagtgactatgtcaagatcctggttgcagctgttgctggcaccata 3311 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 8 : 3237 gtatcctcaccaactagtgactatgtcaagatcctggttgcagctgttgctggcaccata 3296 V. 1 : 3312 actgtcgttgtagttattttcatcactgctgtagtaagatgtcgccaggcaccacacctt 3371 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 8 : 3297 actgtcgttgtagttattttcatcactgctgtagtaagatgtcgccaggcaccacacctt 3356 V. 1 : 3372 aaggctgctcagaaaaacaagcagaattctgaatgggctaccccaaacccagaaaacagg 3431 IIIIIIIIIIIIIIIIIII IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 8 : 3357 aaggctgctcagaaaaacatgcagaattctgaatgggctaccccaaacccagaaaacagg 3416 V. 1 : 3432 cagatgataatgatgaagaaaaagaaaaagaagaagaagcattcccctaagaacttgctg 3491 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII IIIII V. 8 : 3417 cagatgataatgatgaagaaaaagaaaaagaagaagaagcattcccctaagaacctgctg 3476 V. 1 : 3492 cttaattttgtcactattgaagaaactaaggcagatgatgttgacagtgatggaaacaga 3551 IIIIII IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 8 : 3477 cttaatgttgtcactattgaagaaactaaggcagatgatgttgacagtgatggaaacaga 3536 V. 1 : 3552 gtcacactagaccttcctattgatctagaagagcaaacaatgggaaagtacaattgggta 3611 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 8 : 3537 gtcacactagaccttcctattgatctagaagagcaaacaatgggaaagtacaattgggta 3596 V. 1 : 3612 actacacctactactttcaagcccgacagccctgatttggcccgacactacaaatctgcc 3671 IIIIIIIIIIIIIIIIIIIIIII IIIIllllllllllllllllllllllllllllllll V. 8 : 3597 actacacctactactttcaagcctgacagccctgatttggcccgacactacaaatctgcc 3656 V. 1 : 3672 tctccacagcctgccttccaaattcagcctgaaactcccctgaattcgaagcaccacatc 3731 llllllllllllllllllllllllllllllllllllllllllllll IIIIIIIIIIIII V. 8 : 3657 tctccacagcctgccttccaaattcagcctgaaactcccctgaatttgaagcaccacatc 3716 V. 1 : 3732 atccaagaactgcctctcgataacacctttgtggcctgtgactctatctccaagtgttcc 3791 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII IIIIII V. 8 : 3717 atccaagaactgcctctcgataacacctttgtggcctgtgactctatctccaattgttcc 3776 V. 1 : 3792 tcaagcagttcagatccctacagcgtttctgactgtggctatccagtgacgaccttcgag 3851 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII IIIIIIIII V. 8 : 3777 tcaagcagttcagatccctacagcgtttctgactgtggctatccagtgacaaccttcgag 3836 V. 1 : 3852 gtacctgtgtccgtacacaccagaccg 3878 Illllllllllllllllllllllllll V. 8 : 3837 gtacctgtgtccgtacacaccagaccg 3863 Score = 1567 bits (815), Expect = O. OIdentities = 829/836 (99%) Strand = Plus/ Plus V. 1 : 3 ggtggtccagtacctccaaagatatggaatacactcctgaaatatcctgaaaactttttt 62 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII IIIIIII V. 8 : 1 ggtggtccagtacctccaaagatatggaatacactcctgaaatatcctgaaacctttttt 60 V. 1 : 63 ttttcagaatcctttaataagcagttatgtcaatctgaaagttgcttacttgtactttat 122 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 8 : 61 ttttcagaatcctttaataagcagttatgtcaatctgaaagttgcttacttgtactttat 120 V. 1 : 123 attaatagctattcttgtttttcttatccaaagaaaaatcctctaatccccttttcacat 182 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 8 : 121 attaatagctattcttgtttttcttatccaaagaaaaatcctctaatccccttttcacat 180 V. 1 : 183 gatagttgttaccatgtttaggcattagtcacatcaacccctctcctctcccaaacttct 242 IIIIIIIIIIIIIIIIIIIIIII IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 8 : 181 gatagttgttaccatgtttaggcgttagtcacatcaacccctctcctctcccaaacttct 240 V. 1 : 243 cttcttcaaatcaaactttattagtccctcctttataatgattccttgcctcgttttatc 302 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII IIIIIII V. 8 : 241 cttcttcaaatcaaactttattagtccctcctttataatgattccttgcctccttttatc 300 V. 1 : 303 cagatcaattttttttcactttgatgcccagagctgaagaaatggactactgtataaatt 362 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII llllllllll V. 8 : 301 cagatcaattttttttcactttgatgcccagagctgaagaaatggactattgtataaatt 360 V. 1 : 363 attcattgccaagagaataattgcattttaaacccatattataacaaagaataatgatta 422 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII IIIIIIIIIIIIIIIIIIIIII V. 8 : 361 attcattgccaagagaataattgcattttaaacccatgttataacaaagaataatgatta 420 V. 1 : 423 tattttgtgatttgtaacaaataccctttattttcccttaactattgaattaaatatttt 482 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 8 : 421 tattttgtgatttgtaacaaataccctttattttcccttaactattgaattaaatatttt 480 V. 1 : 483 aattatttgtattctctttaactatcttggtatattaaagtattatcttttatatattta 542 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII11111 V. 8 481 aattatttgtattctctttaactatcttggtatattaaagtattatcttttatatattta 540 V. 1 : 543 tcaatggtggacacttttataggtactctgtgtcatttttgatactgtaggtatcttatt 602 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 8 : 541 tcaatggtggacacttttataggtactctgtgtcatttttgatactgtaggtatcttatt 600 V. 1 : 603 tcatttatctttattcttaatgtacgaattcataatatttgattcagaacaaatttatca 662 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII IIIIIIII V. 8 : 601 tcatttatctttattcttaatgtacgaattcataatatttgattcagaacagatttatca 660 V. 1 : 663 ctaattaacagagtgtcaattatgctaacatctcatttactgattttaatttaaaacagt 722 111111111111111111111111111111111111111111111111|11111111111 V. 8 : 661 ctaattaacagagtgtcaattatgctaacatctcatttactgattttaatttaaaacagt 720 V. 1 : 723 ttttgttaacatgcatgtttagggttggcttcttaataatttcttcttcctcttctctct 782 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 8 : 721 ttttgttaacatgcatgtttagggttggcttcttaataatttcttcttcctcttctctct 780 V. 1 : 783 ctcctcttcttttggtcagtgttgtgcgggttaatacaacaaactgtaacaagtgt 838 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII IIIIIIII V. 8 : 781 ctcctcttcttttggtcagtgttgtgcgggttaatacaacaaactgtcacaagtgt 836 Table LIV (g). Peptide sequences of protein coded by 109P1D4 v. 8 (SEQ ID NO : 276) MFRVGFLIIS SSSSLSPLLL VSVVRVNTTN CHKCLLSGTY IFAVLLVCVV FHSGAQEKNY 60 TIREEIPENV LIGNLLKDLN LSLIPNKSLT TTMQFKLVYK TGDVPLIRIE EDTGEIFTTG 120 ARIDREKLCA GIPRDEHCFY EVEVAILPDE IFRLVKIRFL IEDINDNAPL FPATVINISI 180 PENSAINSKY TLPAAVDPDV GINGVQNYEL IKSQNIFGLD VIETPEGDKM PQLIVQKELD 240 REEKDTYVMK VKVEDGGFPQ RSSTAILQVS VTDTNDNHPV FKETEIEVSI PENAPVGTSV 300 TQLHATDADI GENAKIHFSF SNLVSNIARR LFHLNATTGL ITIKEPLDRE ETPNHKLLVL 360 ASDGGLMPAR AMVLVNVTDV NDNVPSIDIR YIVNPVNDTV VLSENIPLNT KIALITVTDK 420 DADHNGRVTC FTDHEIPFRL RPVFSNQFLL ENAAYLDYES TKEYAIKLLA ADAGKPPLNQ 480 SAMLFIKVKD ENDNAPVFTQ SFVTVSIPEN NSPGIQLMKV SATDADSGPN AEINYLLGPD 540 APPEFSLDRR TGMLTVVKKL DREKEDKYLF TILAKDNGVP PLTSNVTVFV SIIDQNDNSP 600 VFTHNEYKFY VPENLPRHGT VGLITVTDPD YGDNSAVTLS ILDENDDFTI DSQTGVIRPN 660 ISFDREKQES YTFYVKAEDG GRVSRSSSAK VTINVVDVND NKPVFIVPPY NYSYELVLPS 720 TNPGTVVFQV IAVDNDTGMN AEVRYSIVGG NTRDLFAIDQ ETGNITLMEK CDVTDLGLHR 780 VLVKANDLGQ PDSLFSVVIV NLFVNESVTN ATLINELVRK SIEAPVTPNT EIADVSSPTS 840 DYVKILVAAV AGTITVVVVI FITAVVRCRQ APHLKAAQKN MQNSEWATPN PENRQMIMMK 900 KKKKKKKHSP KNLLLNVVTI EETKADDVDS DGNRVTLDLP IDLEEQTMGK YNWVTTPTTF 960 KPDSPDLARH YKSASPQPAF QIQPETPLNL KHHIIQELPL DNTFVACDSI SNCSSSSSDP 1020 YSVSDCGYPV TTFEVPVSVH TRPSQRRVTF HLPEGSQESS SDGGLGDHDA GSLTSTSHGL 1080 PLGYPQEEYF DRATPSNRTE GDGNSDPEST FIPGLKKEIT VQPTVEEASD NCTQECLIYG 1140 HSDACWMPAS LDHSSSSQAQ ASALCHSPPL SQASTQHHSP PVTQTIVLCH SPPVTQTIAL 1200 CHSPPPIQVS ALHHSPPLVQ GTALHHSPPS AQASALCYSP PLAQAAAISH SSSLPQVIAL 1260 HRSQAQSSVS LQQGWVQGAN GLCSVDQGVQ GSATSQFYTM SERLHPSDDS IKVIPLTTFA 1320 PRQQARPSRG DSPIMETHPL 1340 Table LV (g). Amino acid sequence alignment of 109P1 D4 v. 1 (SEQ ID NO : 277) and 109P1 D4 v. 8 (SEQ ID NO : 278) Score = 1961 bits (5081), Expect = O. Oldentities = 992/1009 (98%), Positives = 995/1009 (98%) V. 1 : 3 LLSGTYIFAVLLACVVFHSGAQEKNYTIREEMPENVLIGDLLKDLNLSLIPNKSLTTAMQ 62 LLSGTYIFAVLL CWFHSGAQEKNYTIREE+PENVLIG+LLKDLNLSLIPNKSLTT MQ V. 8 : 35 LLSGTYIFAVLLVCWFHSGAQEKNYTIREEIPENVLIGNLLKDLNLSLIPNKSLTTTMQ 94 V. 1 : 63 FKLVYKTGDVPLIRIEEDTGEIFTTGARIDREKLCAGIPRDEHCFYEVEVAILPDEIFRL 122 FKLVYKTGDVPLIRIEEDTGEIFTTGARIDREKLCAGIPRDEHCFYEVEVAILPDEIFRL V. 8 : 95 FKLVYKTGDVPLIRIEEDTGEIFTTGARIDREKLCAGIPRDEHCFYEVEVAILPDEIFRL 154 V. 1 : 123 VKIRFLIEDINDNAPLFPATVINISIPENSAINSKYTLPAAVDPDVGINGVQNYELIKSQ 182 VKIRFLIEDINDNAPLFPATVINISIPENSAINSKYTLPAAVDPDVGINGVQNYELIKSQ V. 8 : 55 VKIRFLIEDINDNAPLFPATVINISIPENSAINSKYTLPAAVDPDVGINGVQNYELIKSQ 214 V. 1 : 183 NIFGLDVIETPEGDKMPQLIVQKELDREEKDTYVMKVKVEDGGFPQRSSTAILQVSVTDT 242 NIFGLDVIETPEGDKMPQLIVQKELDREEKDTYVMKVKVEDGGFPQRSSTAILQVSVTDT V. 8 : 215 NIFGLDVIETPEGDKMPQLIVQKELDREEKDTYVMKVKVEDGGFPQRSSTAILQVSVTDT 274 V. 1 : 243 NDNHPVFKETEIEVSIPENAPVGTSVTQLHATDADIGENAKIHFSFSNLVSNIARRLFHL 302 NDNHPVFKETEIEVSIPENAPVGTSVTQLHATDADIGENAKIHFSFSNLVSNIARRLFHL V. 8 : 275 NDNHPVFKETEIEVSIPENAPVGTSVTQLHATDADIGENAKIHFSFSNLVSNIARRLFHL 334 V. 1 : 303 NATTGLITIKEPLDREETPNHKLLVLASDGGLMPARAMVLVNVTDVNDNVPSIDIRYIVN 362 NATTGLITIKEPLDREETPNHKLLVLASDGGLMPARAMVLVNVTDVNDNVPSIDIRYIVN V. 8 : 335 NATTGLITIKEPLDREETPNHKLLVLASDGGLMPARAMVLVNVTDVNDNVPSIDIRYIVN 394 V. 1 : 363 PVNDTWLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLETAA 422 PVNDTWLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLE AA V. 8 : 395 PVNDTWLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLENAA 454 V. 1 : 423 YLDYESTKEYAIKLLAADAGKPPLNQSAMLFIKVKDENDNAPVFTQSFVTVSIPENNSPG 482 YLDYESTKEYAIKLLAADAGKPPLNQSAMLFIKVKDENDNAPVFTQSFVTVSIPENNSPG V. 8 : 455 YLDYESTKEYAIKLLAADAGKPPLNQSAMLFIKVKDENDNAPVFTQSFVTVSIPENNSPG 514 V. 1 : 483 IQLTKVSAMDADSGPNAKINYLLGPDAPPEFSLDCRTGMLTWKKLDREKEDKYLFTILA 542 IQL KVSA DADSGPNA+INYLLGPDAPPEFSLD RTGMLTWKKLDREKEDKYLFTILA V. 8 : 515 IQLMKVSATDADSGPNAEINYLLGPDAPPEFSLDRRTGMLTWKKLDREKEDKYLFTILA 574 V. 1 : 543 KDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEYNFYVPENLPRHGTVGLITVTDPDYGDN 602 KDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEY FYVPENLPRHGTVGLITVTDPDYGDN V. 8 : 575 KDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEYKFYVPENLPRHGTVGLITVTDPDYGDN 634 V. 1 : 603 SAVTLSILDENDDFTIDSQTGVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVTIN 662 SAVTLSILDENDDFTIDSQTGVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVTIN V. 8 : 635 SAVTLSILDENDDFTIDSQTGVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVTIN 694 V. 1 : 663 WDVNDNKPVFIVPPSNCSYELVLPSTNPGTWFQVIAVDNDTGMNAEVRYSIVGGNTRD 722 VVDVNDNKPVFIVPP N SYELVLPSTNPGTWFQVIAVDNDTGMNAEVRYSIVGGNTRD V. 8 : 695 WDVNDNKPVFIVPPYNYSYELVLPSTNPGTWFQVIAVDNDTGMNAEVRYSIVGGNTRD 754 V. 1 : 723 LFAIDQETGNITLMEKCDVTDLGLHRVLVKANDLGQPDSLFSVVIVNLFVNESVTNATLI 782 LFAIDQETGNITLMEKCDVTDLGLHRVLVKANDLGQPDSLFSWIVNLFVNESVTNATLI V. 8 : 755 LFAIDQETGNITLMEKCDVTDLGLHRVLVKANDLGQPDSLFSWIVNLFVNESVTNATLI 814 V. 1 : 783 NELVRKSTEAPVTPNTEIADVSSPTSDYVKILVAAVAGTITWWIFITAVVRCRQAPHL 842 NELVRKS EAPVTPNTEIADVSSPTSDYVKILVAAVAGTITWWIFITAWRCRQAPHL V. 8 : 815 NELVRKSIEAPVTPNTEIADVSSPTSDYVKILVAAVAGTITWWIFITAWRCRQAPHL 874 V. 1 843 KAAQKNKQNSEWATPNPENRQMIMMKKKKKKKKHSPKNLLLNFVTIEETKADDVDSDGNR 902 KAAQKN QNSEWATPNPENRQMIMMKKKKKKKKHSPKNLLLN VTIEETKADDVDSDGNR V. 8 : 875 KAAQKNMQNSEWATPNPENRQMIMMKKKKKKKKHSPKNLLLNWTIEETKADDVDSDGNR 934 V. 1 : 903 VTLDLPIDLEEQTMGKYNWVTTPTTFKPDSPDLARHYKSASPQPAFQIQPETPLNSKHHI 962 VTLDLPIDLEEQTMGKYNWVTTPTTFKPDSPDLARHYKSASPQPAFQIQPETPLN KHHI V. 8 : 935 VTLDLPIDLEEQTMGKYNWVTTPTTFKPDSPDLARHYKSASPQPAFQIQPETPLNLKHHI 994 V. 1 : 963 IQELPLDNTFVACDSISKCSSSSSDPYSVSDCGYPVTTFEVPVSVHTRP 1011 IQELPLDNTFVACDSIS CSSSSSDPYSVSDCGYPVTTFEVPVSVHTRP V. 8 : 995 IQELPLDNTFVACDSISNCSSSSSDPYSVSDCGYPVTTFEVPVSVHTRP 1043 Table LII (h). Nucleotide sequence of transcript variant 109P1D4 v. 9 (SEQ ID NO : 279) cccctttctc cccctctgtt aagtccctcc ccctcgccat tcaaaagggc tggctcggca 60 ctggctcctt gcagtcggcg aactgtctgg gcgggaggag ccgtgagcag tagctgcact 120 cagctgcccg cgcggcaaag aggaaggcaa gccaaacaga gtgcgcagag tggcagtgcc 180 agcggcgaca caggcagcac aggcagcccg ggctgcctga atagcctcag aaacaacctc 240 agcgactccg gctgctctgc ggactgcgag ctgtggcggt agagcccgct acagcagtcg 300 cagtctccgt ggagcgggcg gaagcctttt ttctcccttt cgtttacctc ttcattctac 360 tctaaaggca tcgttattag gaaaatcctg ttgtgaataa gaaggattcc acagatcaca 420 taccagagcg gttttgcctc agctgctctc aactttgtaa tcttgtgaag aagctgacaa 480 gcttggctga ttgcagtgca ctatgaggac tgaatgacag tgggttttaa ttcagatatt 540 tcaagtgttg tgcgggttaa tacaacaaac tgtcacaagt gtttgttgtc cgggacgtac 600 attttcgcgg tcctgctagt atgcgtggtg ttccactctg gcgcccagga gaaaaactac 660 accatccgag aagaaattcc agaaaacgtc ctgataggca acttgttgaa agaccttaac 720 ttgtcgctga ttccaaacaa gtccttgaca actactatgc agttcaagct agtgtacaag 780 accggagatg tgccactgat tcgaattgaa gaggatactg gtgagatctt cactaccggc 840 gctcgcattg atcgtgagaa attatgtgct ggtatcccaa gggatgagca ttgcttttat 900 gaagtggagg ttgccatttt gccggatgaa atatttagac tggttaagat acgttttctg 960 atagaagata taaatgataa tgcaccattg ttcccagcaa cagttatcaa catatcaatt 1020 ccagagaact cggctataaa ctctaaatat actctcccag cggctgttga tcctgacgta 1080 ggcataaacg gagttcaaaa ctacgaacta attaagagtc aaaacatttt tggcctcgat 1140 gtcattgaaa caccagaagg agacaagatg ccacaactga ttgttcaaaa ggagttagat 1200 agggaagaga aggataccta tgtgatgaaa gtaaaggttg aagatggtgg ctttcctcaa 1260 agatccagta ctgctatttt gcaagtaagt gttactgata caaatgacaa ccacccagtc 1320 tttaaggaga cagagattga agtcagtata ccagaaaatg ctcctgtagg cacttcagtg 1380 acacagctcc atgccacaga tgctgacata ggtgaaaatg ccaagatcca cttctctttc 1440 agcaatctag tctccaacat tgccaggaga ttatttcacc tcaatgccac cactggactt 1500 atcacaatca aagaaccact ggatagggaa gaaacaccaa accacaagtt actggttttg 1560 gcaagtgatg gtggattgat gccagcaaga gcaatggtgc tggtaaatgt tacagatgtc 1620 aatgataatg tcccatccat tgacataaga tacatcgtca atcctgtcaa tgacacagtt 1680 gttctttcag aaaatattcc actcaacacc aaaattgctc tcataactgt gacggataag 1740 gatgcggacc ataatggcag ggtgacatgc ttcacagatc atgaaattcc tttcagatta 1800 aggccagtat tcagtaatca gttcctcctg gagaatgcag catatcttga ctatgagtcc 1860 acaaaagaat atgccattaa attactggct gcagatgctg gcaaacctcc tttgaatcag 1920 tcagcaatgc tcttcatcaa agtgaaagat gaaaatgaca atgctccagt tttcacccag 1980 tctttcgtaa ctgtttctat tcctgagaat aactctcctg gcatccagtt gatgaaagta 2040 agtgcaacgg atgcagacag tgggcctaat gctgagatca attacctgct aggccctgat 2100 gctccacctg aattcagcct ggatcgtcgt acaggcatgc tgactgtagt gaagaaacta 2160 gatagagaaa aagaggataa atatttattc acaattctgg caaaagataa tggggtacca 2220 cccttaacca gcaatgtcac agtctttgta agcattattg atcagaatga caatagccca 2280 gttttcactc acaatgaata caaattctat gtcccagaaa accttccaag gcatggtaca 2340 gtaggactaa tcactgtaac tgatcctgat tatggagaca attctgcagt tacgctctcc 2400 attttagatg agaatgatga cttcaccatt gattcacaaa ctggtgtcat ccgaccaaat 2460 atttcatttg atagagaaaa acaagaatct tacactttct atgtaaaggc tgaggatggt 2520 ggtagagtat cacgttcttc aagtgccaaa gtaaccataa atgtggttga tgtcaatgac 2580 aacaaaccag ttttcattgt ccctccttac aactattctt atgaattggt tctaccgtcc 2640 actaatccag gcacagtggt ctttcaggta attgctgttg acaatgacac tggcatgaat 2700 gcagaggttc gttacagcat tgtaggagga aacacaagag atctgtttgc aatcgaccaa 2760 gaaacaggca acataacatt gatggagaaa tgtgatgtta cagaccttgg tttacacaga 2820 gtgttggtca aagctaatga cttaggacag cctgattctc tcttcagtgt tgtaattgtc 2880 aatctgttcg tgaatgagtc agtgaccaat gctacactga ttaatgaact ggtgcgcaaa 2940 agcattgaag caccagtgac cccaaatact gagatagctg atgtatcctc accaactagt 3000 gactatgtca agatcctggt tgcagctgtt gctggcacca taactgtcgt tgtagttatt 3060 ttcatcactg ctgtagtaag atgtcgccag gcaccacacc ttaaggctgc tcagaaaaac 3120 atgcagaatt ctgaatgggc taccccaaac ccagaaaaca ggcagatgat aatgatgaag 3180 aaaaagaaaa agaagaagaa gcattcccct aagaacctgc tgcttaatgt tgtcactatt 3240 gaagaaacta aggcagatga tgttgacagt gatggaaaca gagtcacact agaccttcct 3300 attgatctag aagagcaaac aatgggaaag tacaattggg taactacacc tactactttc 3360 aagcctgaca gccctgattt ggcccgacac tacaaatctg cctctccaca gcctgccttc 3420 caaattcagc ctgaaactcc cctgaatttg aagcaccaca tcatccaaga actgcctctc 3480 gataacacct ttgtggcctg tgactctatc tccaattgtt cctcaagcag ttcagatccc 3540 tacagcgttt ctgactgtgg ctatccagtg acaaccttcg aggtacctgt gtccgtacac 3600 accagaccga ctgattccag gacatgaact attgaaatct gcagtgagat gtaactttct 3660 aggaacaaca aaattccatt ccccttccaa aaaatttcaa tgattgtgat ttcaaaatta 3720 ggctaagatc attaattttg taatctagat ttcccattat aaaagcaagc aaaaatcatc 3780 ttaaaaatga tgtcctagtg aaccttgtgc tttctttagc tgtaatctgg caatggaaat 3840 ttaaaattta tggaagagac agtgcagcgc aataacagag tactctcatg ctgtttctct 3900 gtttgctctg aatcaacagc catgatgtaa tataaggctg tcttggtgta tacacttatg 3960 gttaatatat cagtcatgaa acatgcaatt acttgccctg tctgattgtt gaataattaa 4020 aacattatct ccaggagttt ggaagtgagc tgaactagcc aaactactct ctgaaaggta 4080 tccagggcaa gagacatttt taagacccca aacaaacaaa aaacaaaacc aaaacactct 4140 ggttcagtgt tttgaaaata ttgactaaca taatattgct gagaaaatca tttttattac 4200 ccaccactct gcttaaaagt tgagtgggcc gggcgcggtg gctcacgcct gtaattccag 4260 cactttggga ggccgaggcg ggtggatcac gaggtcagga tattgagacc atcctggcta 4320 acatggtgaa accccatctc cactaaaaat acaaaaaatt agctgggcgt ggtggcgggc 4380 gcctgtagtc ccagctactc gggaggctga ggcaggagaa tggcgtgaac ccgggaggcg 4440 gagcttgcag tgagccgaga tggcgccact gcactccagc ctgggtgaca gagcaagact 4500 ctgtctcaaa aagaaaaaaa tgttcagtga tagaaaataa ttttactagg tttttatgtt 4560 gattgtactc atgctgttcc actcctttta attattaaaa agttattttt ggctgggtgt 4620 ggtggctcat acctgtaatc ccagcacttt gggaggccga ggcgggtgga tcacctgagg 4680 tcaggagttc aagaccagtc tggccaacat 4710 Table LIII(h). Nucleotide sequence alignment of 109P1D4 v. 1 (SEQ ID NO : 280) and 109P1D4 v. 9 (SEQ ID NO : 281) Score = 5664 bits (2946), Expect = O. Oldentities = 3000/3027 (99%) Strand = Plus/Plus V. 1 : 852 ttgttgtccgggacgtacattttcgcggtcctgctagcatgcgtggtgttccactctggc 911 IIIllllllllllllllllllllllllllllllllll IIIIIIIIIIIIIIIIIIIIII V. 9 : 583 ttgttgtccgggacgtacattttcgcggtcctgctagtatgcgtggtgttccactctggc 642 V. 1 : 912 gcccaggagaaaaactacaccatccgagaagaaatgccagaaaacgtcctgataggcgac 971 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII IIIIIIIIIIIIIIIIIIIII II V. 9 : 643 gcccaggagaaaaactacaccatccgagaagaaattccagaaaacgtcctgataggcaac 702 V. 1 : 972 ttgttgaaagaccttaacttgtcgctgattccaaacaagtccttgacaactgctatgcag 1031 IIIIIIIIIIIIIIIIII. lllllllllllllllllllllllllllllllll IIIIIIII V. 9 : 703 ttgttgaaagaccttaacttgtcgctgattccaaacaagtccttgacaactactatgcag 762 V. 1 : 1032 ttcaagctagtgtacaagaccggagatgtgccactgattcgaattgaagaggatactggt 1091 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 9 : 763 ttcaagctagtgtacaagaccggagatgtgccactgattcgaattgaagaggatactggt 822 V. 1 : 1092 gagatcttcactactggcgctcgcattgatcgtgagaaattatgtgctggtatcccaagg 1151 Illlllllllllll IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 9 : 823 gagatcttcactaccggcgctcgcattgatcgtgagaaattatgtgctggtatcccaagg 882 V. 1 : 1152 gatgagcattgcttttatgaagtggaggttgccattttgccggatgaaatatttagactg 1211 Illlllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 9 : 883 gatgagcattgcttttatgaagtggaggttgccattttgccggatgaaatatttagactg 942 V. 1 : 1212 gttaagatacgttttctgatagaagatataaatgataatgcaccattgttcccagcaaca 1271 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 9 : 943 gttaagatacgttttctgatagaagatataaatgataatgcaccattgttcccagcaaca 1002 V. 1 : 1272 gttatcaacatatcaattccagagaactcggctataaactctaaatatactctcccagcg 1331 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 9 : 1003 gttatcaacatatcaattccagagaactcggctataaactctaaatatactctcccagcg 1062 V. 1 : 1332 gctgttgatcctgacgtaggaataaacggagttcaaaactacgaactaattaagagtcaa 1391 IIIIIIIIIIIIIIIIIIII IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 9 : 1063 gctgttgatcctgacgtaggcataaacggagttcaaaactacgaactaattaagagtcaa 1122 V. 1 : 1392 aacatttttggcctcgatgtcattgaaacaccagaaggagacaagatgccacaactgatt 1451 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 9 : 1123 aacatttttggcctcgatgtcattgaaacaccagaaggagacaagatgccacaactgatt 1182 V. 1 : 1452 gttcaaaaggagttagatagggaagagaaggatacctacgtgatgaaagtaaaggttgaa 1511 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII IIIIIIIIIIIIIIIIIIIII V. 9 : 1183 gttcaaaaggagttagatagggaagagaaggatacctatgtgatgaaagtaaaggttgaa 1242 V. 1 : 1512 gatggtggctttcctcaaagatccagtactgctattttgcaagtgagtgttactgataca 1571 1111111111|111111111111111111111111111111111 111111111111111 V. 9 : 1243 gatggtggctttcctcaaagatccagtactgctattttgcaagtaagtgttactgataca 1302 V. 1 : 1572 aatgacaaccacccagtctttaaggagacagagattgaagtcagtataccagaaaatgct 1631 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 9 : 1303 aatgacaaccacccagtctttaaggagacagagattgaagtcagtataccagaaaatgct 1362 V. 1 : 1632 cctgtaggcacttcagtgacacagctccatgccacagatgctgacataggtgaaaatgcc 1691 Illlllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 9 : 1363 cctgtaggcacttcagtgacacagctccatgccacagatgctgacataggtgaaaatgcc 1422 V. 1 : 1692 aagatccacttctctttcagcaatctagtctccaacattgccaggagattatttcacctc 1751 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 9 : 1423 aagatccacttctctttcagcaatctagtctccaacattgccaggagattatttcacctc 1482 V. 1 : 1752 aatgccaccactggacttatcacaatcaaagaaccactggatagggaagaaacaccaaac 1811 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 9 : 1483 aatgccaccactggacttatcacaatcaaagaaccactggatagggaagaaacaccaaac 1542 V. 1 : 1812 cacaagttactggttttggcaagtgatggtggattgatgccagcaagagcaatggtgctg 1871 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 9 : 1543 cacaagttactggttttggcaagtgatggtggattgatgccagcaagagcaatggtgctg 1602 V. 1 : 1872 gtaaatgttacagatgtcaatgataatgtcccatccattgacataagatacatcgtcaat 1931 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 9 : 1603 gtaaatgttacagatgtcaatgataatgtcccatccattgacataagatacatcgtcaat 1662 V. 1 : 1932 cctgtcaatgacacagttgttctttcagaaaatattccactcaacaccaaaattgctctc 1991 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 9 : 1663 cctgtcaatgacacagttgttctttcagaaaatattccactcaacaccaaaattgctctc 1722 V. 1 : 1992 ataactgtgacggataaggatgcggaccataatggcagggtgacatgcttcacagatcat 2051 lillllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 9 : 1723 ataactgtgacggataaggatgcggaccataatggcagggtgacatgcttcacagatcat 1782 V. 1 : 2052 gaaatccctttcagattaaggccagtattcagtaatcagttcctcctggagactgcagca 2111 IIIII Illllllillllllllllllllllllllllllllllllllllllll IIIIIII V. 9 : 1783 gaaattcctttcagattaaggccagtattcagtaatcagttcctcctggagaatgcagca 1842 V. 1 : 2112 tatcttgactatgagtccacaaaagaatatgccattaaattactggctgcagatgctggc 2171 Illlllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 9 : 1843 tatcttgactatgagtccacaaaagaatatgccattaaattactggctgcagatgctggc 1902 V. 1 : 2172 aaacctcctttgaatcagtcagcaatgctcttcatcaaagtgaaagatgaaaatgacaat 2231 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 9 : 1903 aaacctcctttgaatcagtcagcaatgctcttcatcaaagtgaaagatgaaaatgacaat 1962 V. 1 : 2232 gctccagttttcacccagtctttcgtaactgtttctattcctgagaataactctcctggc 2291 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 9 : 1963 gctccagttttcacccagtctttcgtaactgtttctattcctgagaataactctcctggc 2022 V. 1 : 2292 atccagttgacgaaagtaagtgcaatggatgcagacagtgggcctaatgctaagatcaat 2351 m m m nm m m m n m m m m m m m m nm m n V. 9 : 2023 atccagttgatgaaagtaagtgcaacggatgcagacagtgggcctaatgctgagatcaat 2082 V. 1 : 2352 tacctgctaggccctgatgctccacctgaattcagcctggattgtcgtacaggcatgctg 2411 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII IIIIIIIIIIIIIIIII V. 9 : 2083 tacctgctaggccctgatgctccacctgaattcagcctggatcgtcgtacaggcatgctg 2142 V. 1 : 2412 actgtagtgaagaaactagatagagaaaaagaggataaatatttattcacaattctggca 2471 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 9 : 2143 actgtagtgaagaaactagatagagaaaaagaggataaatatttattcacaattctggca 2202 V. 1 : 2472 aaagataacggggtaccacccttaaccagcaatgtcacagtctttgtaagcattattgat 2531 IIIIIIII Illllllllllllllllllllllllllllllllllllllllllllllllll V. 9 : 2203 aaagataatggggtaccacccttaaccagcaatgtcacagtctttgtaagcattattgat 2262 V. 1 : 2532 cagaatgacaatagcccagttttcactcacaatgaatacaacttctatgtcccagaaaac 2591 Illllllllilllllllllllllllllllllllllllllll IIIIIIIIIIIIIIIIII V. 9 : 2263 cagaatgacaatagcccagttttcactcacaatgaatacaaattctatgtcccagaaaac 2322 V. 1 : 2592 cttccaaggcatggtacagtaggactaatcactgtaactgatcctgattatggagacaat 2651 Illllllllllllllllllllllllllllillllllllllllllllllllllllllllll V. 9 : 2323 cttccaaggcatggtacagtaggactaatcactgtaactgatcctgattatggagacaat 2382 V. 1 : 2652 tctgcagttacgctctccattttagatgagaatgatgacttcaccattgattcacaaact 2711 Illlllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 9 : 2383 tctgcagttacgctctccattttagatgagaatgatgacttcaccattgattcacaaact 2442 V. 1 : 2712 ggtgtcatccgaccaaatatttcatttgatagagaaaaacaagaatcttacactttctat 2771 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 9 : 2443 ggtgtcatccgaccaaatatttcatttgatagagaaaaacaagaatcttacactttctat 2502 V. 1 : 2772 gtaaaggctgaggatggtggtagagtatcacgttcttcaagtgccaaagtaaccataaat 2831 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 9 : 2503 gtaaaggctgaggatggtggtagagtatcacgttcttcaagtgccaaagtaaccataaat 2562 V. 1 : 2832 gtggttgatgtcaatgacaacaaaccagttttcattgtccctccttccaactgttcttat 2891 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII IIIII Illllll V. 9 : 2563 gtggttgatgtcaatgacaacaaaccagttttcattgtccctccttacaactattcttat 2622 V. 1 : 2892 gaattggttctaccgtccactaatccaggcacagtggtctttcaggtaattgctgttgac 2951 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 9 : 2623 gaattggttctaccgtccactaatccaggcacagtggtctttcaggtaattgctgttgac 2682 V. 1 : 2952 aatgacactggcatgaatgcagaggttcgttacagcattgtaggaggaaacacaagagat 3011 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 9 : 2683 aatgacactggcatgaatgcagaggttcgttacagcattgtaggaggaaacacaagagat 2742 V. 1 : 3012 ctgtttgcaatcgaccaagaaacaggcaacataacattgatggagaaatgtgatgttaca 3071 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 9 : 2743 ctgtttgcaatcgaccaagaaacaggcaacataacattgatggagaaatgtgatgttaca 2802 V. 1 : 3072 gaccttggtttacacagagtgttggtcaaagctaatgacttaggacagcctgattctctc 3131 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 9 : 2803 gaccttggtttacacagagtgttggtcaaagctaatgacttaggacagcctgattctctc 2862 V. 1 : 3132 ttcagtgttgtaattgtcaatctgttcgtgaatgagtcggtgaccaatgctacactgatt 3191 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII IIIIIIIIIIIIIIIIIIII V. 9 : 2863 ttcagtgttgtaattgtcaatctgttcgtgaatgagtcagtgaccaatgctacactgatt 2922 V. 1 : 3192 aatgaactggtgcgcaaaagcactgaagcaccagtgaccccaaatactgagatagctgat 3251 Illlllllllllllllllllll IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 9 : 2923 aatgaactggtgcgcaaaagcattgaagcaccagtgaccccaaatactgagatagctgat 2982 V. 1 : 3252 gtatcctcaccaactagtgactatgtcaagatcctggttgcagctgttgctggcaccata 3311 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 9 : 2983 gtatcctcaccaactagtgactatgtcaagatcctggttgcagctgttgctggcaccata 3042 V. 1 : 3312 actgtcgttgtagttattttcatcactgctgtagtaagatgtcgccaggcaccacacctt 3371 Illlllllllllllllllllllllllllllllllllllllllllllllllllllllllll V. 9 : 3043 actgtcgttgtagttattttcatcactgctgtagtaagatgtcgccaggcaccacacctt 3102 V. 1 3372 aaggctgctcagaaaaacaagcagaattctgaatgggctaccccaaacccagaaaacagg 3431 Illllllllllllllllll lllllllllllllllllllllllllllllllllilllll V. 9 : 3103 aaggctgctcagaaaaacatgcagaattctgaatgggctaccccaaacccagaaaacagg 3162 V. 1 : 3432 cagatgataatgatgaagaaaaagaaaaagaagaagaagcattcccctaagaacttgctg 3491 Illlllllllllllllllllllllllllllllllllllllllllllllllllll IIIII V. 9 : 3163 cagatgataatgatgaagaaaaagaaaaagaagaagaagcattcccctaagaacctgctg 3222 V. 1 : 3492 cttaattttgtcactattgaagaaactaaggcagatgatgttgacagtgatggaaacaga 3551 IIIIII IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 9 : 3223 cttaatgttgtcactattgaagaaactaaggcagatgatgttgacagtgatggaaacaga 3282 V. 1 : 3552 gtcacactagaccttcctattgatctagaagagcaaacaatgggaaagtacaattgggta 3611 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 9 : 3283 gtcacactagaccttcctattgatctagaagagcaaacaatgggaaagtacaattgggta 3342 V. 1 : 3612 actacacctactactttcaagcccgacagccctgatttggcccgacactacaaatctgcc 3671 IIIIIIIIIIIIIIIIIIIIIII IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII V. 9 : 3343 actacacctactactttcaagcctgacagccctgatttggcccgacactacaaatctgcc 3402 V. 1 : 3672 tctccacagcctgccttccaaattcagcctgaaactcccctgaattcgaagcaccacatc 3731 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII IIIIIIIIIIIII V. 9 : 3403 tctccacagcctgccttccaaattcagcctgaaactcccctgaatttgaagcaccacatc 3462 V. 1 : 3732 atccaagaactgcctctcgataacacctttgtggcctgtgactctatctccaagtgttcc 3791 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII IIIIII V. 9 : 3463 atccaagaactgcctctcgataacacctttgtggcctgtgactctatctccaattgttcc 3522 V. 1 : 3792 tcaagcagttcagatccctacagcgtttctgactgtggctatccagtgacgaccttcgag 3851 IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII IIIIIIIII V. 9 : 3523 tcaagcagttcagatccctacagcgtttctgactgtggctatccagtgacaaccttcgag 3582 V. 1 : 3852 gtacctgtgtccgtacacaccagaccg 3878 IIIIIIIIIIIIIIIIIIIIIIIIIII V. 9 : 3583 gtacctgtgtccgtacacaccagaccg 3609 Table LIV (h). Peptide sequences of protein coded by 109P1D4v. 9 (SEQ ID NO : 282) MTVGFNSDIS SVVRVNTTNC HKCLLSGTYI FAVLLVCWF HSGAQEKNYT IREEIPENVL 60 IGNLLKDLNL SLIPNKSLTT TMQFKLVYKT GDVPLIRIEE DTGEIFTTGA RIDREKLCAG 120 IPRDEHCFYE VEVAILPDEI FRLVKIRFLI EDINDNAPLF PATVINISIP ENSAINSKYT 180 LPAAVDPDVG INGVQNYELI KSQNIFGLDV IETPEGDKMP QLIVQKELDR EEKDTYVMKV 240 KVEDGGFPQR SSTAILQVSV TDTNDNHPVF KETEIEVSIP ENAPVGTSVT QLHATDADIG 300 ENAKIHFSFS NLVSNIARRL FHLNATTGLI TIKEPLDREE TPNHKLLVLA SDGGLMPARA 360 MVLVNVTDVN DNVPSIDIRY IVNPVNDTW LSENIPLNTK IALITVTDKD ADHNGRVTCF 420 TDHEIPFRLR PVFSNQFLLE NAAYLDYEST KEYAIKLLAA DAGKPPLNQS AMLFIKVKDE 480 NDNAPVFTQS FVTVSIPENN SPGIQLMKVS ATDADSGPNA EINYLLGPDA PPEFSLDRRT 540 GMLTVVKKLD REKEDKYLFT ILAKDNGVPP LTSNVTVFVS IIDQNDNSPV FTHNEYKFYV 600 PENLPRHGTV GLITVTDPDY GDNSAVTLSI LDENDDFTID SQTGVIRPNI SFDREKQESY 660 TFYVKAEDGG RVSRSSSAKV TINWDVNDN KPVFIVPPYN YSYELVLPST NPGTVVFQVI 720 AVDNDTGMNA EVRYSIVGGN TRDLFAIDQE TGNITLMEKC DVTDLGLHRV LVKANDLGQP 780 DSLFSVVIVN LFVNESVTNA TLINELVRKS IEAPVTPNTE IADVSSPTSD YVKILVAAVA 840 GTITVWVIF ITAVVRCRQA PHLKAAQKNM QNSEWATPNP ENRQMIMMKK KKKKKKHSPK 900 NLLLNVVTIE ETKADDVDSD GNRVTLDLPI DLEEQTMGKY NWVTTPTTFK PDSPDLARHY 960 KSASPQPAFQ IQPETPLNLK HHIIQELPLD NTFVACDSIS NCSSSSSDPY SVSDCGYPVT 1020 TFEVPVSVHT RPTDSRT 1037 Table LV (h). Amino acid sequence alignment of 109P1 D4 v. 1 (SEQ ID NO : 283) and 109P1D4 v. 9 (SEQ ID NO : 284) Score = 1961 bits (5081), Expect = O. Oldentities = 992/1009 (98%), Positives = 995/1009 (98%) V. 1 : 3 LLSGTYIFAVLLACVVFHSGAQEKNYTIREEMPENVLIGDLLKDLNLSLIPNKSLTTAMQ 62 LLSGTYIFAVLL CWFHSGAQEKNYTIREE+PENVLIG+LLKDLNLSLIPNKSLTT MQ V. 9 : 24 LLSGTYIFAVLLVCVVFHSGAQEKNYTIREEIPENVLIGNLLKDLNLSLIPNKSLTTTMQ 83 V. 1 : 63 FKLVYKTGDVPLIRIEEDTGEIFTTGARIDREKLCAGIPRDEHCFYEVEVAILPDEIFRL 122 FKLVYKTGDVPLIRIEEDTGEIFTTGARIDREKLCAGIPRDEHCFYEVEVAILPDEIFRL V. 9 : 84 FKLVYKTGDVPLIRIEEDTGEIFTTGARIDREKLCAGIPRDEHCFYEVEVAILPDEIFRL 143 V. 1 : 123 VKIRFLIEDINDNAPLFPATVINISIPENSAINSKYTLPAAVDPDVGINGVQNYELIKSQ 182 VKIRFLIEDINDNAPLFPATVINISIPENSAINSKYTLPAAVDPDVGINGVQNYELIKSQ V. 9 : 144 VKIRFLIEDINDNAPLFPATVINISIPENSAINSKYTLPAAVDPDVGINGVQNYELIKSQ 203 V. 1 : 183 NIFGLDVIETPEGDKMPQLIVQKELDREEKDTYVMKVKVEDGGFPQRSSTAILQVSVTDT 242 NIFGLDVIETPEGDKMPQLIVQKELDREEKDTYVMKVKVEDGGFPQRSSTAILQVSVTDT V. 9 : 204 NIFGLDVIETPEGDKMPQLIVQKELDREEKDTYVMKVKVEDGGFPQRSSTAILQVSVTDT 263 V. 1 : 243 NDNHPVFKETEIEVSIPENAPVGTSVTQLHATDADIGENAKIHFSFSNLVSNIARRLFHL 302 NDNHPVFKETEIEVSIPENAPVGTSVTQLHATDADIGENAKIHFSFSNLVSNIARRLFHL V. 9 : 264 NDNHPVFKETEIEVSIPENAPVGTSVTQLHATDADIGENAKIHFSFSNLVSNIARRLFHL 323 V. 1 : 303 NATTGLITIKEPLDREETPNHKLLVLASDGGLMPARAMVLVNVTDVNDNVPSIDIRYIVN 362 NATTGLITIKEPLDREETPNHKLLVLASDGGLMPARAMVLVNVTDVNDNVPSIDIRYIVN V. 9 : 324 NATTGLITIKEPLDREETPNHKLLVLASDGGLMPARAMVLVNVTDVNDNVPSIDIRYIVN 383 V. 1 : 363 PVNDTWLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLETAA 422 PVNDTWLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLE AA V. 9 : 384 PVNDTWLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLENAA 443 V. 1 : 423 YLDYESTKEYAIKLLAADAGKPPLNQSAMLFIKVKDENDNAPVFTQSFVTVSIPENNSPG 482 YLDYESTKEYAIKLLAADAGKPPLNQSAMLFIKVKDENDNAPVFTQSFVTVSIPENNSPG V. 9 : 444 YLDYESTKEYAIKLLAADAGKPPLNQSAMLFIKVKDENDNAPVFTQSFVTVSIPENNSPG 503 V. 1 : 483 IQLTKVSAMDADSGPNAKINYLLGPDAPPEFSLDCRTGMLTVVKKLDREKEDKYLFTILA 542 IQL KVSA DADSGPNA+INYLLGPDAPPEFSLD RTGMLTWKKLDREKEDKYLFTILA V. 9 : 504 IQLMKVSATDADSGPNAEINYLLGPDAPPEFSLDRRTGMLTWKKLDREKEDKYLFTILA 563 V. 1 : 543 KDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEYNFYVPENLPRHGTVGLITVTDPDYGDN 602 KDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEY FYVPENLPRHGTVGLITVTDPDYGDN V. 9 : 564 KDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEYKFYVPENLPRHGTVGLITVTDPDYGDN 623 V. 1 : 603 SAVTLSILDENDDFTIDSQTGVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVTIN 662 SAVTLSILDENDDFTIDSQTGVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVTIN V. 9 : 624 SAVTLSILDENDDFTIDSQTGVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVTIN 683 V. 1 : 663 WDVNDNKPVFIVPPSNCSYELVLPSTNPGTWFQVIAVDNDTGMNAEVRYSIVGGNTRD 722 WDVNDNKPVFIVPP N SYELVLPSTNPGTWFQVIAVDNDTGMNAEVRYSIVGGNTRD V. 9 : 684 WDVNDNKPVFIVPPYNYSYELVLPSTNPGTWFQVIAVDNDTGMNAEVRYSIVGGNTRD 743 V. 1 : 723 LFAIDQETGNITLMEKCDVTDLGLHRVLVKANDLGQPDSLFSWIVNLFVNESVTNATLI 782 LFAIDQETGNITLMEKCDVTDLGLHRVLVKANDLGQPDSLFSWIVNLFVNESVTNATLI V. 9 : 744 LFAIDQETGNITLMEKCDVTDLGLHRVLVKANDLGQPDSLFSWIVNLFVNESVTNATLI 803 V. 1 : 783 NELVRKSTEAPVTPNTEIADVSSPTSDYVKILVAAVAGTITWWIFITAWRCRQAPHL 842 NELVRKS EAPVTPNTEIADVSSPTSDYVKILVAAVAGTITWWIFITAWRCRQAPHL V. 9 : 804 NELVRKSIEAPVTPNTEIADVSSPTSDYVKILVAAVAGTITWWIFITAWRCRQAPHL 863 V. 1 : 843 KAAQKNKQNSEWATPNPENRQMIMMKKKKKKKKHSPKNLLLNFVTIEETKADDVDSDGNR 902 KAAQKN QNSEWATPNPENRQMIMMKKKKKKKKHSPKNLLLN VTIEETKADDVDSDGNR V. 9 : 864 KAAQKNMQNSEWATPNPENRQMIMMKKKKKKKKHSPKNLLLNVVTIEETKADDVDSDGNR 923 V. 1 : 903 VTLDLPIDLEEQTMGKYNWVTTPTTFKPDSPDLARHYKSASPQPAFQIQPETPLNSKHHI 962 VTLDLPIDLEEQTMGKYNWVTTPTTFKPDSPDLARHYKSASPQPAFQIQPETPLN KHHI V. 9 : 924 VTLDLPIDLEEQTMGKYNWVTTPTTFKPDSPDLARHYKSASPQPAFQIQPETPLNLKHHI 983 V. 1 : 963 IQELPLDNTFVACDSISKCSSSSSDPYSVSDCGYPVTTFEVPVSVHTRP 1011 IQELPLDNTFVACDSIS CSSSSSDPYSVSDCGYPVTTFEVPVSVHTRP V. 9 : 984 IQELPLDNTFVACDSISNCSSSSSDPYSVSDCGYPVTTFEVPVSVHTRP 1032