THE EFFECT OF CLASS-II MAJOR HISTOCOMPATIBILITY COMPLEX EXPRESSION ONADHERENCE OF HELICOBACTER-PYLORI AND INDUCTION OF APOPTOSIS IN GASTRIC EPITHELIAL-CELLS - A MECHANISM FOR T-HELPER CELL-TYPE 1-MEDIATED DAMAGE

Helicobacter pylori infection is associated with gastric epithelial da mage, including apoptosis, ulceration, and cancer. Although bacterial factors and the host response are believed to contribute to gastric di sease, no receptor has been identified that explains how the bacteria attach and signal the host cell to undergo apoptosis. Using H. pylori as ''bait'' to capture receptor proteins in solubilized membranes of g astric epithelial cells, class II major histocompatibility complex (MH C) molecules were identified as a possible receptor. Signaling through class II MHC molecules leading to the induction of apoptosis was conf irmed using cross-linking IgM antibodies to surface class II MHC molec ules. Moreover, binding of H. pylori and the induction of apoptosis we re inhibited by antibodies recognizing class II MHC. Since type 1 T he lper cells are present during infection and produce interferon (IFN)-g amma, which increases class II MHC expression, gastric epithelial cell lines were exposed to H. pylori in the presence or absence of IFN-gam ma. IFN-gamma increased the attachment of the bacteria as well as the induction of apoptosis in gastric epithelial cells. In contrast to MHC II-negative cell lines, H. pylori induced apoptosis in cells expressi ng class II MHC molecules constitutively or after gene transfection. T hese data describe a novel receptor for H. pylori and provide a mechan ism by which bacteria and the host response interact in the pathogenes is of gastric epithelial cell damage.