7n2p

Publication Abstract from PubMed

Human leucocyte antigen B*27 (HLA-B*27) is strongly associated with inflammatory diseases of the spine and pelvis (for example, ankylosing spondylitis (AS)) and the eye (that is, acute anterior uveitis (AAU))(1). How HLA-B*27 facilitates disease remains unknown, but one possible mechanism could involve presentation of pathogenic peptides to CD8(+) T cells. Here we isolated orphan T cell receptors (TCRs) expressing a disease-associated public beta-chain variable region-complementary-determining region 3beta (BV9-CDR3beta) motif(2-4) from blood and synovial fluid T cells from individuals with AS and from the eye in individuals with AAU. These TCRs showed consistent alpha-chain variable region (AV21) chain pairing and were clonally expanded in the joint and eye. We used HLA-B*27:05 yeast display peptide libraries to identify shared self-peptides and microbial peptides that activated the AS- and AAU-derived TCRs. Structural analysis revealed that TCR cross-reactivity for peptide-MHC was rooted in a shared binding motif present in both self-antigens and microbial antigens that engages the BV9-CDR3beta TCRs. These findings support the hypothesis that microbial antigens and self-antigens could play a pathogenic role in HLA-B*27-associated disease.

Autoimmunity-associated T cell receptors recognize HLA-B*27-bound peptides.,Yang X, Garner LI, Zvyagin IV, Paley MA, Komech EA, Jude KM, Zhao X, Fernandes RA, Hassman LM, Paley GL, Savvides CS, Brackenridge S, Quastel MN, Chudakov DM, Bowness P, Yokoyama WM, McMichael AJ, Gillespie GM, Garcia KC Nature. 2022 Dec;612(7941):771-777. doi: 10.1038/s41586-022-05501-7. Epub 2022 , Dec 7. PMID:36477533^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.