DELIVERY OF ANTIGENS TO THE MHC CLASS-I PATHWAY USING BACTERIAL TOXINS

Cytotoxic T lymphocytes (CTL) recognize antigens derived from endogeno usly expressed proteins presented on the cell surface in the concert o f major histocompatibility complex (MHC) class I molecules. Because CT L are effective in antiviral and antitumor responses, the delivery of antigens to the class I pathway has been the focus of numerous efforts . Generating CTL by immunization with exogenous proteins is often inef fective because these antigens typically enter the MHC class II pathwa y. This review focuses on the usefulness of bacterial toxins for deliv ering antigens to the MHC class I pathway. Several toxins naturally tr anslocate into the cytosol, where they mediate their cytopathic effect s, and the mechanisms by which this occurs has been elucidated. Molecu lar characterization of these toxins identified the functional domains and enabled the generation of modified proteins that were no longer t oxic but retained the ability to translocate into the cytosol. Thus, t hese modified toxins could be examined for their ability to carry pept ides or whole proteins into che cytosolic processing pathway. Of the t oxins studied-diphtheria, pertussis, Pseudomonas, and anthrax-the anth rax toxin appears the most promising in its ability to deliver large p rotein antigens and its efficiency of translocation.