Projects per year
Abstract
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.
Original language | English |
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Article number | e1005549 |
Pages (from-to) | 1 |
Number of pages | 25 |
Journal | PLoS pathogens |
Volume | 12 |
Issue number | 4 |
DOIs | |
Publication status | Published - 20 Apr 2016 |
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Dive into the research topics of 'Early T Cell Recognition of B Cells following Epstein-Barr Virus Infection: Identifying Potential Targets for Prophylactic Vaccination'. Together they form a unique fingerprint.Projects
- 2 Finished
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Molecular and Cellular Mechanisms of Synapse-Mediated Spread of Epstein Barr Virus: Overcoming the CD21-Restricted Cellular Tropism
Shannon-Lowe, C. (Principal Investigator)
1/09/12 → 29/02/16
Project: Research Councils
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Cellular Immunity to Herpesvirus Infections: Studies with Epstein-Barr Virus (EBV) and Human Cytomegalovirus (CMV)
Rickinson, A. (Principal Investigator), Moss, P. (Co-Investigator) & Rowe, M. (Co-Investigator)
1/09/10 → 31/08/15
Project: Research Councils