The effect of class II major histocompatibility complex expression on adherence 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 damage, including apoptosis, ulceration, and cancer. Although bacterial factors and the host response are believed to contribute to gastric disease, 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 gastric epithelial cells, class II major histocompatibility complex (MHC) molecules were identified as a possible receptor. Signaling through class II MHC molecules leading to the induction of apoptosis was confirmed using cross-linking IgM antibodies to surface class II MHC molecules. Moreover, binding of H. pylori and the induction of apoptosis were inhibited by antibodies recognizing class II MHC. Since type 1 T helper cells are present during infection and produce interferon (IFN)-gamma, which increases class II MHC expression, gastric epithelial cell lines were exposed to H. pylori in the presence or absence of IFN-gamma. 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 expressing class II MHC molecules constitutively or after gene transfection. These data describe a novel receptor for H. pylori and provide a mechanism by which bacteria and the host response interact in the pathogenesis of gastric epithelial cell damage.
Fan
X
X
Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas 77555, USA.
Crowe
S E
SE
Behar
S
S
Gunasena
H
H
Ye
G
G
Haeberle
H
H
Van Houten
N
N
Gourley
W K
WK
Ernst
P B
PB
Reyes
V E
VE
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D019556:COS Cells; D005753:Gastric Mucosa / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D016481:Helicobacter Infections / Q000276:immunology* / Q000473:pathology; D016480:Helicobacter pylori / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*
D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma