A shared TCR bias toward an immunogenic EBV epitope dominates in HLA-B*07: 02-Expressing individuals

Louise C. Rowntree, Thi H. O. Nguyen, Carine Farenc, Hanim Halim, Luca Hensen, Jamie Rossjohn, Tom C. Kotsimbos, Anthony W. Purcell, Katherine Kedzierska, Stephanie Gras, Nicole A. Mifsud

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4 Citations (Scopus)


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 [EBVRPP]). However, little is known about either the TCR repertoire specific for this epitope or the molecular basis for this observed immunodominance. The EBVRPP CD8+ T cell response was common among both EBV-seropositive HLA-B*07:02+ healthy and immunocompromised individuals. Similar TCRs were identified in EBVRPP-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/EBVRPP 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.

Original languageEnglish
Pages (from-to)1524-1534
Number of pages11
JournalJournal of Immunology
Issue number6
Publication statusPublished - 15 Sep 2020

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