%0 Journal Article
%A Gonzalez-Duque, Sergio
%A Azoury, Marie Eliane
%A Colli, Maikel L
%A Afonso, Georgia
%A Turatsinze, Jean-Valery
%A Nigi, Laura
%A Lalanne, Ana Ines
%A Sebastiani, Guido
%A Carré, Alexia
%A Pinto, Sheena
%A Culina, Slobodan
%A Corcos, Noémie
%A Bugliani, Marco
%A Marchetti, Piero
%A Armanet, Mathieu
%A Diedisheim, Marc
%A Kyewski, Bruno
%A Steinmetz, Lars M
%A Buus, Søren
%A You, Sylvaine
%A Dubois-Laforgue, Daniele
%A Larger, Etienne
%A Beressi, Jean-Paul
%A Bruno, Graziella
%A Dotta, Francesco
%A Scharfmann, Raphael
%A Eizirik, Decio L
%A Verdier, Yann
%A Vinh, Joelle
%A Mallone, Roberto
%T Conventional and Neo-antigenic Peptides Presented by β Cells Are Targeted by Circulating Naïve CD8+ T Cells in Type 1 Diabetic and Healthy Donors.
%J Cell metabolism
%V 28
%N 6
%@ 1550-4131
%C Cambridge, Mass.
%I Cell Press
%M DKFZ-2018-02268
%P 946 - 960.e6
%D 2018
%X 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:30078552
%R 10.1016/j.cmet.2018.07.007
%U https://inrepo02.dkfz.de/record/142038