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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, 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: 30 Oct 2020 12:30
URI: http://orca.cf.ac.uk/id/eprint/136024

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