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Herpesviridae. 2011 Feb 11;2(1):4. doi: 10.1186/2042-4280-2-4.

Cytolytic T lymphocytes from HLA-B8+ donors frequently recognize the Hodgkin's lymphoma associated latent membrane protein 2 of Epstein Barr virus.

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  • 1Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, USA. christian.muenz@uzh.ch.

Abstract

Epstein Barr virus (EBV) is a lymphotrophic γ-herpesvirus that infects more than 90% of the adult human population. It transforms B cells in vitro and is associated with lymphomas in vivo. In most EBV carriers the emergence of these malignancies, however, is prevented by T cell mediated immune control. Part of this control is mediated by CD8+ T cells, which mainly target a subset of viral nuclear antigens, EBNA3A, B and C, in healthy EBV carriers. In HLA-B8 positive individuals, the dominant CTL response is biased towards recognition of EBNA3A. However, spontaneously arising EBV-associated malignancies, such as Hodgkin's lymphoma and nasopharyngeal carcinoma do not express EBNA3s and instead express latent membrane protein 2 (LMP2) as well as LMP1 and EBNA1. Here we describe the new HLA-B8 restricted, LMP2 derived CD8+ T cell epitope, LMP2345-352. Although the frequency of LMP2345-352 specific CD8+ T cells is usually lower than immunodominant EBNA3A specific CD8+ T cells in fresh blood, the former can be expanded in the majority of HLA-B8+ EBV carriers after 1 week co-culture with peptide pulsed dendritic cells. We demonstrate that LMP2345-352 specific CD8+ T cells secrete IFN-γ and kill both peptide pulsed targets as well as HLA-B8 matched LCL and LMP2 expressing Hodgkin's lymphoma cells. We suggest that cytotoxic CD8+ T cell responses against LMP2 coexist with the immunodominant EBNA3 specific responses in healthy EBV carriers and help to resist EBV associated malignancies.

PMID:
21429247
PMCID:
PMC3063197
DOI:
10.1186/2042-4280-2-4
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