How C-terminal additions to insulin B-chain fragments create superagonists for T cells in mouse and human type 1 diabetes.

ABSTRACT: In type 1 diabetes (T1D), proinsulin is a major autoantigen and the insulin B:9-23 peptide contains epitopes for CD4⁺ T cells in both mice and humans. This peptide requires carboxyl-terminal mutations for uniform binding in the proper position within the mouse IA^g7 or human DQ8 major histocompatibility complex (MHC) class II (MHCII) peptide grooves and for strong CD4⁺ T cell stimulation. Here, we present crystal structures showing how these mutations control CD4⁺ T cell receptor (TCR) binding to these MHCII-peptide complexes. Our data reveal stricking similarities between mouse and human CD4⁺ TCRs in their interactions with these ligands. We also show how fusions between fragments of B:9-23 and of proinsulin C-peptide create chimeric p

SUBMITTER: Wang Y 

PROVIDER: S-EPMC6929690 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature