Conventional and Neo-antigenic Peptides Presented by beta Cells Are Targeted by Circulating Naive CD8+T Cells in Type 1 Diabetic and Healthy Donors

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Sergio Gonzalez-Duque
  • Marie Eliane Azoury
  • Maikel L. Colli
  • Georgia Afonso
  • Jean-Valery Turatsinze
  • Laura Nigi
  • Ana Ines Lalanne
  • Guido Sebastiani
  • Alexia Carre
  • Sheena Pinto
  • Slobodan Culina
  • Noemie Corcos
  • Marco Bugliani
  • Piero Marchetti
  • Mathieu Armanet
  • Marc Diedisheim
  • Bruno Kyewski
  • Lars M. Steinmetz
  • Sylvaine You
  • Daniele Dubois-Laforgue
  • Etienne Larger
  • Jean-Paul Beressi
  • Graziella Bruno
  • Francesco Dotta
  • Raphael Scharfmann
  • Decio L. Eizirik
  • Yann Verdier
  • Joelle Vinh
  • Roberto Mallone
Although CD8 + T-cell-mediated autoimmune β cell destruction occurs in type 1 diabetes (T1D), the target epitopes processed and presented by β cells are unknown. To identify them, we combined peptidomics and transcriptomics strategies. Inflammatory cytokines increased peptide presentation in vitro, paralleling upregulation of human leukocyte antigen (HLA) class I expression. Peptide sources featured several insulin granule proteins and all known β cell antigens, barring islet-specific glucose-6-phosphatase catalytic subunit-related protein. Preproinsulin yielded HLA-A2-restricted epitopes previously described. Secretogranin V and its mRNA splice isoform SCG5-009, proconvertase-2, urocortin-3, the insulin gene enhancer protein ISL-1, and an islet amyloid polypeptide transpeptidation product emerged as antigens processed into HLA-A2-restricted epitopes, which, as those already described, were recognized by circulating naive CD8 + T cells in T1D and healthy donors and by pancreas-infiltrating cells in T1D donors. This peptidome opens new avenues to understand antigen processing by β cells and for the development of T cell biomarkers and tolerogenic vaccination strategies.
TidsskriftCell Metabolism
Udgave nummer6
Sider (fra-til)946-960
StatusUdgivet - 2018

ID: 212859916