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

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...

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Bibliographic Details
Published in:	Scientific reports Vol. 3; no. 1; p. 3232
Main Authors:	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, Lee, Kok Onn, Loh, Thomas Kwok Seng, Chen, Jianzhu, Chan, Soh Ha, MacAry, Paul Anthony
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 18-11-2013 Nature Publishing Group
Subjects:	13/31 13/51 14 631/250/21 631/250/580 82/1 Animals Antibodies, Monoclonal - immunology Antigens, Viral - immunology CD8-Positive T-Lymphocytes - immunology Cell Line, Tumor Epitopes Epitopes, T-Lymphocyte - immunology Epstein-Barr virus Epstein-Barr Virus Infections - immunology Epstein-Barr Virus Nuclear Antigens - immunology Genes Herpesvirus 4, Human - immunology HLA-A2 Antigen - immunology Humanities and Social Sciences Humans Immunology Immunotherapy Infections Lymphocytes Lymphocytes T Mice Mice, Inbred BALB C Mice, Inbred NOD Mice, SCID multidisciplinary Receptors, Antigen, T-Cell - immunology Science Viral Matrix Proteins - immunology Virus Latency - immunology
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2045-2322 2045-2322
DOI:	10.1038/srep03232