Helicobacter pylori urease binds to class II MHC on gastric epithelial cells and induces their apoptosis.
Infection by Helicobacter pylori leads to injury of the gastric epithelium and a cellular infiltrate that includes CD4+ T cells. H. pylori binds to class II MHC molecules on gastric epithelial cells and induces their apoptosis. Because urease is an abundant protein expressed by H. pylori, we examined whether it had the ability to bind class II MHC and induce apoptosis in class II MHC-bearing cells. Flow cytometry revealed the binding of PE-conjugated urease to class II MHC+ gastric epithelial cell lines. The binding of urease to human gastric epithelial cells was reduced by anti-class II MHC Abs and by staphylococcal enterotoxin B. The binding of urease to class II MHC was confirmed when urease bound to HLA-DR1-transfected COS-1 (1D12) cells but not to untransfected COS-1 cells. Urease also bound to a panel of B cell lines expressing various class II MHC alleles. Recombinant urease induced apoptosis in gastric epithelial cells that express class II MHC molecules, but not in class II MHC- cells. Also, Fab from anti-class II MHC and not from isotype control Abs blocked the induction of apoptosis by urease in a concentration-dependent manner. The adhesin properties of urease might point to a novel and important role of H. pylori urease in the pathogenesis of H. pylori infection.
Fan
X
X
Departments of Pediatrics, Internal Medicine, and Microbiology and Immunology, and the Sealy Center for Molecular Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA.
Gunasena
H
H
Cheng
Z
Z
Espejo
R
R
Crowe
S E
SE
Ernst
P B
PB
Reyes
V E
VE
D000483:Alleles; D017209:Apoptosis / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D001665:Binding Sites / Q000276:immunology; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D002846:Chromatography, Affinity; D004847:Epithelial Cells / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D005753:Gastric Mucosa / Q000166:cytology / Q000201:enzymology* / Q000276:immunology / Q000382:microbiology*; D006683:HLA-DQ Antigens / Q000096:biosynthesis / Q000235:genetics; D006684:HLA-DR Antigens / Q000096:biosynthesis / Q000235:genetics; D016480:Helicobacter pylori / Q000201:enzymology*; D000949:Histocompatibility Antigens Class II / Q000302:isolation & purification / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D014407:Tumor Cells, Cultured; D014510:Urease / Q000276:immunology / Q000378:metabolism* / Q000502:physiology
D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D014510:Urease