A Shared TCR Bias toward an Immunogenic EBV Epitope Dominates in HLA-B*07:02-Expressing Individuals.
J Immunol
; 205(6): 1524-1534, 2020 09 15.
Article
in En
| MEDLINE
| ID: mdl-32817371
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*0702 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*0702+ 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*0702/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*0702+ individuals.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Herpesvirus 4, Human
/
CD8-Positive T-Lymphocytes
/
Epstein-Barr Virus Infections
Type of study:
Prognostic_studies
Limits:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
J Immunol
Year:
2020
Type:
Article
Affiliation country:
Australia