Autoimmunity-associated T cell receptors recognize HLA-B*27-bound peptides

Abstract

HLA-B27 is strongly linked to axial spondyloarthritis and acute anterior uveitis, yet the pathogenic mechanisms connecting this allele to disease have remained elusive. In this work, the authors isolate public CD8⁺ T cell receptors bearing a characteristic BV9–CDR3β motif from blood, synovial fluid, and ocular samples of affected individuals. Using HLA-B27:05 yeast-display peptide libraries, they identify shared self and microbial peptides that activate these disease-associated TCRs and determine the structures of the resulting peptide–HLA–TCR complexes. The structural data reveal a common binding motif that underlies cross-recognition of self and microbial antigens, supporting a model in which molecular mimicry between gut-derived microbes and self-peptides contributes to HLA-B*27–associated autoimmunity.