Defining the expression hierarchy of latent T-cell epitopes in Epstein-Barr virus infection with TCR-like antibodies
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Author(s) • • • • • • • • •
Sim, Adrian Chong Nyi
Too, Chien Tei
Oo, Min Zin
Lai, Junyun
Eio, Michelle Yating
Song, Zhenying
Srinivasan, Nalini
Tan, Diane Ai Lin
Pang, Shyue Wei
Gan, Shu Uin
Date Issued
November 2013
Journal
Scientific Reports
Publisher
Nature Publishing Group
Citation
Sim, Adrian Chong Nyi, Chien Tei Too, Min Zin Oo, Junyun Lai, Michelle Yating Eio, Zhenying Song, Nalini Srinivasan, et al. “Defining the Expression Hierarchy of Latent T-Cell Epitopes in Epstein-Barr Virus Infection with TCR-Like Antibodies.” Sci. Rep. 3 (November 18, 2013).
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Final published version
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[subscript 125–133], LMP2A[subscript 426–434] or EBNA1[subscript 562–570] in association with HLA-A0201. These are employed to map the expression hierarchy of endogenously generated EBV epitopes. The dominance of EBNA1[subscript 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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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DOI of Published Version
https://doi.org/10.1038/srep03232