Early T Cell Recognition of B Cells following Epstein-Barr Virus Infection: Identifying Potential Targets for Prophylactic Vaccination

PLoS Pathogens

Martin Fitzpatrick¹  Rose J. Tierney²  Alan B. Rickinson²  Jill M. Brooks²  Claire Shannon-Lowe³  Alison M. Leese³  Heather M. Long³  Graham S. Taylor³ 

[1] Biomolecular Mass Spectrometry and Proteomics Group, Utrecht University, Utrecht, The Netherlands;Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, United Kingdom;Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom

关键词: T cells;    B cells;    Cytotoxic T cells;    Antigen processing;    recognition;    Immune response;    Lytic cycle;    Enzyme-linked immunoassays;    Gene expression;   

DOI  :  10.1371/journal.ppat.1005549

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Epstein-Barr virus, a B-lymphotropic herpesvirus, is the cause of infectious mononucleosis, has strong aetiologic links with several malignancies and has been implicated in certain autoimmune diseases. Efforts to develop a prophylactic vaccine to prevent or reduce EBV-associated disease have, to date, focused on the induction of neutralising antibody responses. However, such vaccines might be further improved by inducing T cell responses capable of recognising and killing recently-infected B cells. In that context, EBNA2, EBNA-LP and BHRF1 are the first viral antigens expressed during the initial stage of B cell growth transformation, yet have been poorly characterised as CD8+ T cell targets. Here we describe CD8+ T cell responses against each of these three “first wave” proteins, identifying target epitopes and HLA restricting alleles. While EBNA-LP and BHRF1 each contained one strong CD8 epitope, epitopes within EBNA2 induced immunodominant responses through several less common HLA class I alleles (e.g. B*3801 and B*5501), as well as subdominant responses through common class I alleles (e.g. B7 and C*0304). Importantly, such EBNA2-specific CD8+ T cells recognised B cells within the first day post-infection, prior to CD8+ T cells against well-characterised latent target antigens such as EBNA3B or LMP2, and effectively inhibited outgrowth of EBV-transformed B cell lines. We infer that “first wave” antigens of the growth-transforming infection, especially EBNA2, constitute potential CD8+ T cell immunogens for inclusion in prophylactic EBV vaccine design.

【 授权许可】

CC BY