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 apopto sis,Because urease is an abundant protein expressed by H, pylori, we examin ed 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-conju gated 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-I (1D12) cel ls but not to untransfected COS-1 cells. Urease also bound to a panel of B cell lines expressing various class II MBC alleles. Recombinant urease indu ced apoptosis in gastric epithelial cells that express class II MHC molecul es, but not in class II MHC- cells. Also, Fab from anti-class II MHC and no t from isotype control Abs blocked the induction of apoptosis by urease in a concentration-dependent manner. The adhesin properties of urease might po int to a novel and important role of H, pylori urease in the pathogenesis o f H, pylori infection.