Press-room / news / Science news /

Identification of HLA-B*27-bound peptides recognized by TCRs associated with ankylosing spondylitis

Ankylosing spondylitis is an autoimmune rheumatological disease, where aberrant immune response against self-antigens is considered as a main trigger of the pathology. Up to date identification of antigen epitopes recognized by specific T cell receptors (TCRs), especially self-epitopes, remains tricky challenge and there is the very limited list of TCRs with characterized antigen specificity.

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

Previously in the Laboratory of comparative and functional genomics of Shemyakin-Ovchinnikov institute of bioorganic chemistry RAS we described the full amino acid sequence of a TCR associated with ankylosing spondylitis (AS). Collaborative efforts of researchers from Universities of Stanford and Oxford, as wells as Washington University of St. Louis and Shemyakin-Ovchinnikov institute of bioorganic chemistry, allowed to reveal sequence of several other AS-related TCRs and describe the peptide motif recognized by such TCRs. Structural analysis of TCRpMHC complexes allowed to identify shared binding motif present in both self-antigens and microbial antigens that engages AS-related TCRs. These findings support the hypothesis that cross-reactivity between microbial and self-antigens can be considered as a trigger event for pathogenesis of ankylosing spondylitis. Deciphering of antigen-specificity of the AS-related TCRs allows studying of the role of such T cells in pathogenesis and development of new therapeutic approaches for ankylosing spondylitis. The results of the study have been recently published in Nature.

december 13, 2022