6VMX

Structure of HD14 TCR in complex with HLA-B7 presenting an EBV epitope

Summary for 6VMX

• Entry DOI: 10.2210/pdb6vmx/pdb
• Descriptor: HLA class I histocompatibility antigen, B-7 alpha chain, Beta-2-microglobulin, Epstein-Barr nuclear antigen 3, ... (8 entities in total)
• Functional Keywords: tcr, mhc, ebv, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 10
• Total formula weight: 191264.67

Authors

Farenc, C.,Rossjohn, J.,Gras, S. (deposition date: 2020-01-28, release date: 2020-07-29, Last modification date: 2024-11-06)

Primary citation

Rowntree, L.C.,Nguyen, T.H.O.,Farenc, C.,Halim, H.,Hensen, L.,Rossjohn, J.,Kotsimbos, T.C.,Purcell, A.W.,Kedzierska, K.,Gras, S.,Mifsud, N.A.
A Shared TCR Bias toward an Immunogenic EBV Epitope Dominates in HLA-B*07:02-Expressing Individuals.
J Immunol., 205:1524-1534, 2020

PubMed Abstract: EBV is one of the most common viruses found in humans and is prototypic of a persistent viral infection characterized by periods of latency. Across many HLA class I molecules, the latent-specific CD8 T cell response is focused on epitopes derived from the EBNA-3 protein family. In the case of HLA-B*07:02 restriction, a highly frequent class I allele, the T cell response is dominated by an epitope spanning residues 379-387 of EBNA-3 (RPPIFIRRL [EBV]). However, little is known about either the TCR repertoire specific for this epitope or the molecular basis for this observed immunodominance. The EBV CD8 T cell response was common among both EBV-seropositive HLA-B*07:02 healthy and immunocompromised individuals. Similar TCRs were identified in EBV-specific CD8 T cell repertoires across multiple HLA-B7 individuals, indicating a shared Ag-driven bias in TCR usage. In particular, TRBV4-1 and TRAV38 usage was observed in five out of six individuals studied. In this study, we report the crystal structure of a TRBV4-1 TCR-HLA-B*07:02/EBV complex, which provides a molecular basis for the observed TRBV4-1 bias. These findings enhance our understanding of the CD8 T cell response toward a common EBV determinant in HLA-B*07:02 individuals.

PubMed: 32817371
DOI: 10.4049/jimmunol.2000249

Experimental method

X-RAY DIFFRACTION (3.1 Å)