TY  - JOUR
AU  - Gonzalez-Duque, Sergio
AU  - Azoury, Marie Eliane
AU  - Colli, Maikel L
AU  - Afonso, Georgia
AU  - Turatsinze, Jean-Valery
AU  - Nigi, Laura
AU  - Lalanne, Ana Ines
AU  - Sebastiani, Guido
AU  - Carré, Alexia
AU  - Pinto, Sheena
AU  - Culina, Slobodan
AU  - Corcos, Noémie
AU  - Bugliani, Marco
AU  - Marchetti, Piero
AU  - Armanet, Mathieu
AU  - Diedisheim, Marc
AU  - Kyewski, Bruno
AU  - Steinmetz, Lars M
AU  - Buus, Søren
AU  - You, Sylvaine
AU  - Dubois-Laforgue, Daniele
AU  - Larger, Etienne
AU  - Beressi, Jean-Paul
AU  - Bruno, Graziella
AU  - Dotta, Francesco
AU  - Scharfmann, Raphael
AU  - Eizirik, Decio L
AU  - Verdier, Yann
AU  - Vinh, Joelle
AU  - Mallone, Roberto
TI  - Conventional and Neo-antigenic Peptides Presented by β Cells Are Targeted by Circulating Naïve CD8+ T Cells in Type 1 Diabetic and Healthy Donors.
JO  - Cell metabolism
VL  - 28
IS  - 6
SN  - 1550-4131
CY  - Cambridge, Mass.
PB  - Cell Press
M1  - DKFZ-2018-02268
SP  - 946 - 960.e6
PY  - 2018
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:30078552
DO  - DOI:10.1016/j.cmet.2018.07.007
UR  - https://inrepo02.dkfz.de/record/142038
ER  -