%0 Journal Article
%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.
%A Gonzalez-Duque S
%A Azoury ME
%A Colli ML
%A Afonso G
%A Turatsinze JV
%A Nigi L
%A Lalanne AI
%A Sebastiani G
%A Carré A
%A Pinto S
%A Culina S
%A Corcos N
%A Bugliani M
%A Marchetti P
%A Armanet M
%A Diedisheim M
%A Kyewski B
%A Steinmetz LM
%A Buus S
%A You S
%A Dubois-Laforgue D
%A Larger E
%A Beressi JP
%A Bruno G
%A Dotta F
%A Scharfmann R
%A Eizirik DL
%A Verdier Y
%A Vinh J
%A Mallone R
%J Cell Metab
%V 28
%N 6
%D 12 2018 4
%M 30078552
%F 31.373
%R 10.1016/j.cmet.2018.07.007
%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.