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

Autor: Sim AC; 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]., Too CT, Oo MZ, Lai J, Eio MY, Song Z, Srinivasan N, Tan DA, Pang SW, Gan SU, Lee KO, Loh TK, Chen J, Chan SH, MacAry PA
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2013 Nov 18; Vol. 3, pp. 3232. Date of Electronic Publication: 2013 Nov 18.
DOI: 10.1038/srep03232
Abstrakt: 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.
Databáze: MEDLINE