8TRR

T cell recognition of citrullinated vimentin peptide presented by HLA-DR4

Summary for 8TRR

• Entry DOI: 10.2210/pdb8trr/pdb
• Descriptor: HLA class II histocompatibility antigen, DR alpha chain, 2-acetamido-2-deoxy-beta-D-glucopyranose, HLA class II histocompatibility antigen, DRB1 beta chain, ... (11 entities in total)
• Functional Keywords: immune receptor complex, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 10
• Total formula weight: 194488.40

Authors

Loh, T.J.,Lim, J.J.,Reid, H.H.,Rossjohn, J. (deposition date: 2023-08-10, release date: 2024-07-31, Last modification date: 2024-10-09)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.65 Å)