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Journal of Virology, April 2003, p. 4298-4305, Vol. 77, No. 7
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.7.4298-4305.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

The B Subunit of Escherichia coli Heat-Labile Enterotoxin Enhances CD8⁺ Cytotoxic-T-Lymphocyte Killing of Epstein-Barr Virus-Infected Cell Lines

Kong-Wee Ong, A. Douglas Wilson, Timothy R. Hirst, and Andrew J. Morgan^*

Department of Pathology and Microbiology, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom

Received 12 November 2002/ Accepted 2 January 2003

Epstein-Barr virus (EBV) is associated with a number of important human cancers, including nasopharyngeal carcinoma, gastric carcinoma, and Hodgkin's lymphoma. These tumors express a viral nuclear antigen, EBV nuclear antigen 1 (EBNA1), which cannot be presented to T cells in a major histocompatibility complex class I context, and the viral latent membrane proteins (LMPs). Although the LMPs are expressed in these tumors, no effective immune response is made. We report here that exposure to the cholera-like enterotoxin B subunit (EtxB) in EBV-infected lymphoblastoid cell lines (LCLs) enhances their susceptibility to killing by LMP-specific CD8⁺ cytotoxic T lymphocytes (CTLs) in a HLA class I-restricted manner. CTL killing of LCLs is dramatically increased through both transporter-associated protein-dependent and -independent epitopes after EtxB treatment. The use of mutant B subunits revealed that the enhanced susceptibility of LCLs to CTL killing is dependent on the B subunit's interaction with GM₁ but not its signaling properties. These important findings could underpin the development of novel approaches to treating EBV-associated malignancies and may offer a general approach to increasing the presentation of other tumor and viral antigens.

Present address: Division of Cellular and Molecular Research, National Cancer Centre, Singapore 169610.

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