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Publication Abstract from PubMed

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.

A Shared TCR Bias toward an Immunogenic EBV Epitope Dominates in HLA-B*07:02-Expressing Individuals.,Rowntree LC, Nguyen THO, Farenc C, Halim H, Hensen L, Rossjohn J, Kotsimbos TC, Purcell AW, Kedzierska K, Gras S, Mifsud NA J Immunol. 2020 Sep 15;205(6):1524-1534. doi: 10.4049/jimmunol.2000249. Epub 2020, Aug 19. PMID:32817371^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.