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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology*
  • Antigens, Viral / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Line, Tumor
  • Epitopes, T-Lymphocyte / immunology*
  • Epstein-Barr Virus Infections / immunology*
  • Epstein-Barr Virus Nuclear Antigens / immunology
  • HLA-A2 Antigen / immunology
  • Herpesvirus 4, Human / immunology*
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred NOD
  • Mice, SCID
  • Receptors, Antigen, T-Cell / immunology*
  • Viral Matrix Proteins / immunology
  • Virus Latency / immunology*


  • Antibodies, Monoclonal
  • Antigens, Viral
  • EBV-associated membrane antigen, Epstein-Barr virus
  • Epitopes, T-Lymphocyte
  • Epstein-Barr Virus Nuclear Antigens
  • HLA-A*02:01 antigen
  • HLA-A2 Antigen
  • Receptors, Antigen, T-Cell
  • Viral Matrix Proteins
  • EBV-encoded nuclear antigen 1