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Sci Rep. 2013 Nov 18;3:3232. doi: 10.1038/srep03232.

Defining the expression hierarchy of latent T-cell epitopes in Epstein-Barr virus infection with TCR-like antibodies.

Author information

1
1] Immunology Program, Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117456, Singapore [2] NUS Graduate School of Integrative Sciences and Engineering (NGS), National University of Singapore, Singapore 117456, Singapore [3].

Abstract

Epstein-Barr virus (EBV) is a gamma herpesvirus that causes a life-long latent infection in human hosts. The latent gene products LMP1, LMP2A and EBNA1 are expressed by EBV-associated tumors and peptide epitopes derived from these can be targeted by CD8 Cytotoxic T-Lymphocyte (CTL) lines. Whilst CTL-based methodologies can be utilized to infer the presence of specific latent epitopes, they do not allow a direct visualization or quantitation of these epitopes. Here, we describe the characterization of three TCR-like monoclonal antibodies (mAbs) targeting the latent epitopes LMP1(125-133), LMP2A(426-434) or EBNA1(562-570) in association with HLA-A0201. These are employed to map the expression hierarchy of endogenously generated EBV epitopes. The dominance of EBNA1(562-570) in association with HLA-A0201 was consistently observed in cell lines and EBV-associated tumor biopsies. These data highlight the discordance between MHC-epitope density and frequencies of associated CTL with implications for cell-based immunotherapies and/or vaccines for EBV-associated disease.

PMID:
24240815
PMCID:
PMC3831236
DOI:
10.1038/srep03232
[Indexed for MEDLINE]
Free PMC Article

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