The molecular basis of T cell receptor recognition of citrullinated tenascin-C presented by HLA-DR4.

ABSTRACT: CD4⁺ T cell autoreactivity against citrullinated (cit) self-epitopes presented by HLA-DRB1 is associated with rheumatoid arthritis (RA) pathogenesis. We understand the molecular bases of T cell receptor (TCR) recognition of cit-fibrinogen, cit-vimentin, and cit-α-enolase epitopes, and the role of citrulline in shaping TCR repertoire usage. Nevertheless, how TCRs recognize other cit-epitopes, including tenascin-C (TNC) and how alternative citrullination positions may modulate the T cell recognition remains unclear. Here, we examined TNC^1014,1016cit peptide, which contains citrullination at position P-1 and P2, to study the underlying TCR-HLA-DRB1^∗04:01-TNC^1014,1016cit molecular interactions. Crystal structure of HLA-DRB1^∗04:01^TNC10

SUBMITTER: Dao HT 

PROVIDER: S-EPMC12269843 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature