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Title: Defining the expression hierarchy of latent T-cell epitopes in Epstein-Barr virus infection with TCR-like antibodies
Authors: Sim A.C.N. 
Too C.T. 
Oo M.Z. 
Lai J. 
Eio M.Y.
Song Z.
Srinivasan N.
Tan D.A.L. 
Pang S.W.
Gan S.U. 
Lee K.O. 
Loh T.K.S. 
Chen J. 
Chan S.H. 
Macary P.A. 
Keywords: EBV-associated membrane antigen, Epstein-Barr virus
EBV-encoded nuclear antigen 1
Epstein Barr virus antigen
HLA A2 antigen
HLA-A*02:01 antigen
lymphocyte antigen receptor
matrix protein
monoclonal antibody
virus antigen
Bagg albino mouse
CD8+ T lymphocyte
Epstein Barr virus
Epstein Barr virus infection
nonobese diabetic mouse
SCID mouse
tumor cell line
virus latency
Antibodies, Monoclonal
Antigens, Viral
CD8-Positive T-Lymphocytes
Cell Line, Tumor
Epitopes, T-Lymphocyte
Epstein-Barr Virus Infections
Epstein-Barr Virus Nuclear Antigens
Herpesvirus 4, Human
HLA-A2 Antigen
Mice, Inbred BALB C
Mice, Inbred NOD
Mice, SCID
Receptors, Antigen, T-Cell
Viral Matrix Proteins
Virus Latency
Issue Date: 2013
Citation: Sim A.C.N., Too C.T., Oo M.Z., Lai J., Eio M.Y., Song Z., Srinivasan N., Tan D.A.L., Pang S.W., Gan S.U., Lee K.O., Loh T.K.S., Chen J., Chan S.H., Macary P.A. (2013). Defining the expression hierarchy of latent T-cell epitopes in Epstein-Barr virus infection with TCR-like antibodies. Scientific Reports 3 : 3232. ScholarBank@NUS Repository.
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.
Source Title: Scientific Reports
ISSN: 2045-2322
DOI: 10.1038/srep03232
Appears in Collections:Staff Publications

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