HLA autoimmune risk alleles restrict the hypervariable region of T cell receptors.

ABSTRACT: Polymorphisms in the human leukocyte antigen (HLA) genes strongly influence autoimmune disease risk. HLA risk alleles may influence thymic selection to increase the frequency of T cell receptors (TCRs) reactive to autoantigens (central hypothesis). However, research in human autoimmunity has provided little evidence supporting the central hypothesis. Here we investigated the influence of HLA alleles on TCR composition at the highly diverse complementarity determining region 3 (CDR3), which confers antigen recognition. We observed unexpectedly strong HLA-CDR3 associations. The strongest association was found at HLA-DRB1 amino acid position 13, the position that mediates genetic risk for multiple autoimmune diseases. We identified multiple CDR3 amino acid features enriched by HLA risk allele

SUBMITTER: Ishigaki K 

PROVIDER: S-EPMC9010379 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature