8TRL

T cell recognition of citrullinated alpha-enolase peptide presented by HLA-DR4

8TRL の概要

• エントリーDOI: 10.2210/pdb8trl/pdb
• 分子名称: HLA class II histocompatibility antigen, DR alpha chain, FORMIC ACID, GLYCEROL, ... (12 entities in total)
• 機能のキーワード: immune receptor complex, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 195605.05

構造登録者

Lim, J.J.,Loh, T.J.,Reid, H.H.,Rossjohn, J. (登録日: 2023-08-09, 公開日: 2024-07-31, 最終更新日: 2024-11-13)

主引用文献

Loh, T.J.,Lim, J.J.,Jones, C.M.,Dao, H.T.,Tran, M.T.,Baker, D.G.,La Gruta, N.L.,Reid, H.H.,Rossjohn, J.
The molecular basis underlying T cell specificity towards citrullinated epitopes presented by HLA-DR4.
Nat Commun, 15:6201-6201, 2024

PubMed 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 and α-enolase-15cit 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 epitope. Moreover, shared TRAV26-1 gene usage is evident in four α-enolase-15cit reactive T cells in three human samples. Crystal structures of mouse TRAV6 and human TRAV26-1 TCR-HLA-DR4 complexes presenting vimentin-64cit and α-enolase-15cit, respectively, show three-way interactions between the TCR, SE, citrulline, and the basis for the biased selection of TRAV genes. Position 2 of the citrullinated epitope is a key determinant underpinning TCR specificity. Accordingly, we provide a molecular basis of TCR specificity towards citrullinated epitopes.

PubMed: 39043656
DOI: 10.1038/s41467-024-50511-w

実験手法

X-RAY DIFFRACTION (2.4 Å)