Peptides derived from insulin granule proteins are targeted by CD8+ T cells across MHC Class I restrictions in humans and NOD mice

• DOI: 10.2337/figshare.12899315.v1
• Publication Date: 2020-09-14T18:51:27Z
• Authors: Ada Admin; Marie Eliane Azoury; Mahmoud Tarayrah; Georgia Afonso; Aurore Pais; Maikel L. Colli; Claire Maillard; Cassandra Lavaud; Laure Alexandre-H...; Sergio Gonzalez-D...; Yann Verdier; Joelle Vinh; Sheena Pinto; Soren Buus; Danièle Dubois-La...; Etienne Larger; Jean-Paul Beressi; Graziella Bruno; Decio L. Eizirik; Sylvaine You; Roberto Mallone
• Keywords: NOD mice

The antigenic peptides processed by β cells and presented through surface HLA Class I molecules are poorly characterized. Each variant, e.g. the most common HLA-A2 HLA-A3, carries some peptide-binding specificity. Hence, features that, despite these specificities, remain shared across variants may reveal factors favoring β-cell immunogenicity. Building on our previous description of HLA-A2/A3 peptidome cells, we analyzed HLA-A3-restricted targeted circulating CD8<sup>+</sup> T cells. Several were recognized within a narrow frequency (1-50/10<sup>6</sup>), which was similar in donors with without type 1 diabetes harbored variable effector/memory fractions. These epitopes could be classified as conventional or neo-epitopes, generated either via peptide <i>cis</i>-splicing mRNA splicing, secretogranin-5 (SCG5)-009. As reported for HLA-A2-restricted peptides, several originated from granule proteins, SCG3, SCG5 urocortin-3. Similarly, H-2K<sup>d</sup>-restricted recognizing murine orthologues SCG5, urocortin-3, proconvertase-2 infiltrated islets NOD mice transferred into NOD/<i>scid</i> recipients. finding proteins both humans supports their disease relevance identifies insulin rich source epitopes, possibly reflecting its impaired processing diabetes.