[PDF][PDF] Conventional and neo-antigenic peptides presented by β cells are targeted by circulating naïve CD8+ T cells in type 1 diabetic and healthy donors

S Gonzalez-Duque, ME Azoury, ML Colli, G Afonso… - Cell metabolism, 2018 - cell.com
S Gonzalez-Duque, ME Azoury, ML Colli, G Afonso, JV Turatsinze, L Nigi, AI Lalanne…
Cell metabolism, 2018cell.com
Summary 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 …
Summary
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.
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