{Reference Type}: Journal Article
{Title}: Conventional and Neo-antigenic Peptides Presented by β Cells Are Targeted by Circulating Naïve CD8+ T Cells in Type 1 Diabetic and Healthy Donors.
{Author}: Gonzalez-Duque S;Azoury ME;Colli ML;Afonso G;Turatsinze JV;Nigi L;Lalanne AI;Sebastiani G;Carré A;Pinto S;Culina S;Corcos N;Bugliani M;Marchetti P;Armanet M;Diedisheim M;Kyewski B;Steinmetz LM;Buus S;You S;Dubois-Laforgue D;Larger E;Beressi JP;Bruno G;Dotta F;Scharfmann R;Eizirik DL;Verdier Y;Vinh J;Mallone R;
{Journal}: Cell Metab
{Volume}: 28
{Issue}: 6
{Year}: 12 2018 4
{Factor}: 31.373
{DOI}: 10.1016/j.cmet.2018.07.007
{Abstract}: 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.