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

Research output: Contribution to journalArticleResearchpeer-review

4 Citations (Scopus)

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 [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
Volume205
Issue number6
DOIs
Publication statusPublished - 15 Sep 2020

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