The molecular basis underlying T cell specificity towards citrullinated epitopes presented by HLA-DR4.

ABSTRACT: CD4⁺ T cells recognising citrullinated self-epitopes presented by HLA-DRB1 bearing the shared susceptibility epitope (SE) are implicated in rheumatoid arthritis (RA). However, the underlying T cell receptor (TCR) determinants of epitope specificity towards distinct citrullinated peptide antigens, including vimentin-64cit_59-71 and α-enolase-15cit_10-22 remain unclear. Using HLA-DR4-tetramers, we examine the T cell repertoire in HLA-DR4 transgenic mice and observe biased TRAV6 TCR gene usage across these two citrullinated epitopes which matches with TCR bias previously observed towards the fibrinogen β-74cit_69-81 epitope. Moreover, shared TRAV26-1 gene usage is evident in four α-enolase-15cit_10-22 reactive T cells in three human samples.

SUBMITTER: Loh TJ 

PROVIDER: S-EPMC11266596 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature