Research ArticleAUTOIMMUNITY

Position β57 of I-Ag7 controls early anti-insulin responses in NOD mice, linking an MHC susceptibility allele to type 1 diabetes onset

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Science Immunology  30 Aug 2019:
Vol. 4, Issue 38, eaaw6329
DOI: 10.1126/sciimmunol.aaw6329

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Insulin peptide recognition by early diabetogenic T cells

Type 1 diabetes is initiated by loss of T cell tolerance to pancreatic islet autoantigens including insulin. Gioia et al. developed peptide-MHC tetramer reagents capable of distinguishing separate populations of insulin-reactive CD4+ T cells from diabetes-prone NOD mice that differ in the register used for insulin peptide binding to class II MHC. Analysis of pancreatic islet tissue using these tetramers revealed that the earliest phase of the anti-insulin T cell response in islets is dominated by T cells with TCR sequence modifications that enable recognition of an Ins12–20 peptide–MHC class II complex. Identification of the primary mode of peptide recognition used by the early anti-insulin T cells opens the door to designing inhibitors capable of selectively blocking activation of these rogue T cells.

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