{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Gioia L"],"funding":["National Institutes of Health"],"pagination":["eaaw6329"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6816460"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["4(38)"],"pubmed_abstract":["The class II region of the major histocompatibility complex (MHC) locus is the main contributor to the genetic susceptibility to type 1 diabetes (T1D). The loss of an aspartic acid at position 57 of diabetogenic HLA-DQβ chains supports this association; this single amino acid change influences how TCRs recognize peptides in the context of HLA-DQ8 and I-Ag7 using a mechanism termed the P9 switch. Here, we built register-specific insulin peptide MHC tetramers to examine CD4+ T cell responses to Ins12-20 and Ins13-21 peptides during the early prediabetic phase of disease in nonobese diabetic (NOD) mice. A single-cell analysis of anti-insulin CD4+ T cells performed in 6- and 12-week-old NOD mice revealed tissue-specific gene expression signatures. TCR signaling and clonal expansion were found "],"journal":["Science immunology"],"pubmed_title":["Position β57 of I-Ag7 controls early anti-insulin responses in NOD mice, linking an MHC susceptibility allele to type 1 diabetes onset."],"pmcid":["PMC6816460"],"funding_grant_id":["UL1TR002550, TL1TR002551","1R01DK117138","R01DK099317","DK097605 and DK107541","RO1DK058177","UL1TR002550, KL2TR001112"],"pubmed_authors":["Sharma S","Abe B","Kain L","Su A","Gioia L","Mathews C","Unanue E","Wan X","Holt M","Chen YG","Costanzo A","Teyton L","Nakayama M"],"additional_accession":[]},"is_claimable":false,"name":"Position β57 of I-Ag7 controls early anti-insulin responses in NOD mice, linking an MHC susceptibility allele to type 1 diabetes onset.","description":"The class II region of the major histocompatibility complex (MHC) locus is the main contributor to the genetic susceptibility to type 1 diabetes (T1D). The loss of an aspartic acid at position 57 of diabetogenic HLA-DQβ chains supports this association; this single amino acid change influences how TCRs recognize peptides in the context of HLA-DQ8 and I-Ag7 using a mechanism termed the P9 switch. Here, we built register-specific insulin peptide MHC tetramers to examine CD4+ T cell responses to Ins12-20 and Ins13-21 peptides during the early prediabetic phase of disease in nonobese diabetic (NOD) mice. A single-cell analysis of anti-insulin CD4+ T cells performed in 6- and 12-week-old NOD mice revealed tissue-specific gene expression signatures. TCR signaling and clonal expansion were found ","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Aug","modification":"2025-05-31T23:54:08.726Z","creation":"2025-05-31T23:54:08.726Z"},"accession":"S-EPMC6816460","cross_references":{"pubmed":["31471352"],"doi":["10.1126/sciimmunol.aaw6329"]}}