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Title:
ANTIGENIC PEPTIDES DERIVING FROM UROCORTIN 3 AND USES THEREOF FOR THE DIAGNOSIS AND TREATMENT OF TYPE 1 DIABETES
Document Type and Number:
WIPO Patent Application WO/2019/175384
Kind Code:
A3
Abstract:
Despite the notion that human CD8+ T cells are the final mediators of autoimmune β-cell destruction in type 1 diabetes (T1D), none of their target epitopes has been demonstrated to be naturally processed and presented by β cells. The inventors therefore performed an epitope discovery study combining HLA Class I peptidomics and transcriptomics strategies. Inflammatory cytokines increased β-cell peptide presentation in vitro, paralleling upregulation of HLA Class I expression. Peptide sources included known β-cell antigens and several insulin granule proteins. Urocortin 3 was identified as a novel β-cell antigen, which was processed into HLA-A2- and HLA- A3 -restricted epitopes recognized by circulating naive CD8+ T cells in type 1 diabetic and healthy donors. Accordingly, the present invention relates to antigenic peptides derived from urocortin-3 and uses thereof for the diagnosis and treatment of T1D.

Inventors:
MALLONE ROBERTO (FR)
GONZALEZ-DUQUE SERGIO (FR)
VERDIER YANN (FR)
AZOURY MARIE-ELIANE (FR)
AFONSO GEORGIA (FR)
VINH JOËLLE (FR)
Application Number:
PCT/EP2019/056543
Publication Date:
October 24, 2019
Filing Date:
March 15, 2019
Export Citation:
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Assignee:
INST NAT SANTE RECH MED (FR)
UNIV PARIS DESCARTES (FR)
CENTRE NAT RECH SCIENT (FR)
ECOLE SUPERIEURE PHYSIQUE & CHIMIE IND VILLE DE PARIS (FR)
International Classes:
A61K38/00; A61K38/22; C07K7/08; C07K14/435; C07K14/47; C07K14/705
Domestic Patent References:
WO2016146751A12016-09-22
Other References:
LI CHIEN ET AL: "Urocortin 3 regulates glucose-stimulated insulin secretion and energy homeostasis", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, NATIONAL ACADEMY OF SCIENCES, US, vol. 104, no. 10, 6 March 2007 (2007-03-06), pages 4206 - 4211, XP009166234, ISSN: 0027-8424, DOI: 10.1073/PNAS.0611641104
SERGIO GONZALEZ-DUQUE ET AL: "Conventional and Neo-Antigenic Peptides Presented by [beta] Cells Are Targeted by Circulating Naïve CD8+ T Cells in Type 1 Diabetic and Healthy Donors", CELL METABOLISM, 1 August 2018 (2018-08-01), United States, XP055514994, ISSN: 1550-4131, DOI: 10.1016/j.cmet.2018.07.007
Attorney, Agent or Firm:
INSERM TRANSFERT (FR)
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