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-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.
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].
Adrian Chong Nyi
AC
Sim
Chien Tei
CT
Too
Min Zin
MZ
Oo
Junyun
J
Lai
Michelle Yating
MY
Eio
Zhenying
Z
Song
Nalini
N
Srinivasan
Diane Ai Lin
DA
Tan
Shyue Wei
SW
Pang
Shu Uin
SU
Gan
Kok Onn
KO
Lee
Thomas Kwok Seng
TK
Loh
Jianzhu
J
Chen
Soh Ha
SH
Chan
Paul Anthony
PA
MacAry
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D045744:Cell Line, Tumor; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D020031:Epstein-Barr Virus Infections / Q000276:immunology*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology; D015789:HLA-A2 Antigen / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000276:immunology; D017735:Virus Latency / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000956:Antigens, Viral; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D018984:Epitopes, T-Lymphocyte; D019309:Epstein-Barr Virus Nuclear Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D011948:Receptors, Antigen, T-Cell; D014763:Viral Matrix Proteins; C417029:EBV-encoded nuclear antigen 1