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

Rowntree, Louise C., Nguyen, Thi H. O., Farenc, Carine, Halim, Hanim, Hensen, Luca, Rossjohn, Jamie ORCID: https://orcid.org/0000-0002-2020-7522, Kotsimbos, Tom C., Purcell, Anthony W., Kedzierska, Katherine, Gras, Stephanie and Mifsud, Nicole A. 2020. A shared TCR bias toward an immunogenic EBV epitope dominates in HLA-B*07:02–expressing individuals. Journal of Immunology 205 (6) , pp. 1524-1534. 10.4049/jimmunol.2000249

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	American Association of Immunologists
ISSN:	0022-1767
Date of Acceptance:	19 July 2020
Last Modified:	09 Nov 2022 09:31
URI:	https://orca.cardiff.ac.uk/id/eprint/136024

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