A structural basis of T cell cross-reactivity to native and spliced self-antigens presented by HLA-DQ8.

ABSTRACT: Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease that has a strong HLA association, where a number of self-epitopes have been implicated in disease pathogenesis. Human pancreatic islet-infiltrating CD4⁺ T cell clones not only respond to proinsulin C-peptide (PI_40-54; GQVELGGGPGAGSLQ) but also cross-react with a hybrid insulin peptide (HIP; PI_40-47-IAPP_74-80; GQVELGGG-NAVEVLK) presented by HLA-DQ8. How T cell receptors recognize self-peptide and cross-react to HIPs is unclear. We investigated the cross-reactivity of the CD4⁺ T cell clones reactive to native PI_40-54 epitope and multiple HIPs fused at the same N-terminus (PI_40-54) to the degradation products of two highly expressed pancreatic islet prote

SUBMITTER: Tran MT 

PROVIDER: S-EPMC11388500 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature