g(m1)-ganglioside and Epstein-Barr-Virus-Infections

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.

Topics: Amino Acid Sequence; Antigen Presentation; Bacterial Toxins; Cell Line; Cell Membrane; Cysteine Endopeptidases; Cytotoxicity, Immunologic; Enterotoxins; Epitopes; Epstein-Barr Virus Infections; Escherichia coli Proteins; G(M1) Ganglioside; Herpesvirus 4, Human; Histocompatibility Antigens Class I; Humans; Multienzyme Complexes; Proteasome Endopeptidase Complex; Signal Transduction; T-Lymphocytes, Cytotoxic; Viral Matrix Proteins