2. Academic Validation
  3. A Shared TCR Bias toward an Immunogenic EBV Epitope Dominates in HLA-B*07:02-Expressing Individuals

A Shared TCR Bias toward an Immunogenic EBV Epitope Dominates in HLA-B*07:02-Expressing Individuals

  • J Immunol. 2020 Sep 15;205(6):1524-1534. doi: 10.4049/jimmunol.2000249.
Louise C Rowntree 1 2 3,  Thi H O Nguyen 4,  Carine Farenc 3 5,  Hanim Halim 3,  Luca Hensen 4,  Jamie Rossjohn 3 5 6,  Tom C Kotsimbos 1 2,  Anthony W Purcell 3,  Katherine Kedzierska 4,  Stephanie Gras 3 5,  Nicole A Mifsud 7 2 3
Affiliations

Affiliations

  • 1 Department of Medicine, Monash University, Central Clinical School, The Alfred Hospital, Melbourne, Victoria 3004, Australia.
  • 2 Department of Allergy, Immunology, and Respiratory Medicine, The Alfred Hospital, Melbourne, Victoria 3004, Australia.
  • 3 Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.
  • 4 Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010, Australia.
  • 5 Australian Research Council Centre of Excellence for Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia; and.
  • 6 Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff CF14 4XN, United Kingdom.
  • 7 Department of Medicine, Monash University, Central Clinical School, The Alfred Hospital, Melbourne, Victoria 3004, Australia; anthony.purcell@monash.edu.
PMID: 32817371 DOI: 10.4049/jimmunol.2000249
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.

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