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Ong, KW, Wilson, AD, Hirst, TR and Morgan, AJ (2003) The B subunit of Escherichia coli heat-labile enterotoxin enhances CD8+ cytotoxic-T-lymphocyte killing of Epstein-Barr virus-infected cell lines. J. Virol. 77:4298-305
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 GM(1) 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.
Amino Acid Sequence; Antigen Presentation/drug effects; Bacterial Toxins/immunology; Bacterial Toxins/pharmacology; Cell Line; Cell Membrane/drug effects; Cell Membrane/immunology; Cell Membrane/virology; Cysteine Endopeptidases/metabolism; Cytotoxicity, Immunologic; Enterotoxins/immunology; Enterotoxins/pharmacology; Epitopes/genetics; Epstein-Barr Virus Infections/immunology; Epstein-Barr Virus Infections/therapy; Escherichia coli Proteins; G(M1) Ganglioside/metabolism; Herpesvirus 4, Human/genetics; Herpesvirus 4, Human/immunology; Histocompatibility Antigens Class I/metabolism; Humans; Multienzyme Complexes/metabolism; Proteasome Endopeptidase Complex; Signal Transduction; T-Lymphocytes, Cytotoxic/drug effects; T-Lymphocytes, Cytotoxic/immunology; Viral Matrix Proteins/genetics; Viral Matrix Proteins/metabolism
|Gene product||Qualifier||GO Term||Evidence Code||with/from||Aspect||Extension||Notes||Status|
|GO:0031640 : killing of cells of other organism||
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