Molecular Mimicry between Helicobacter pylori Antigens and H⁺,K⁺–Adenosine Triphosphatase in Human Gastric Autoimmunity

Autoimmune gastritis and Helicobacter pylori–associated gastric atrophy develop through similar mechanisms involving the proton pump H⁺,K⁺–adenosine triphosphatase as autoantigen. Here, we report that H. pylori–infected patients with gastric autoimmunity harbor in vivo–activated gastric CD4⁺ T cells that recognize both H⁺,K⁺–adenosine triphosphatase and H. pylori antigens. We characterized the submolecular specificity of such gastric T cells and identified cross-reactive epitopes from nine H. pylori proteins. Cross-reactive H. pylori peptides induced T cell proliferation and expression of T helper type 1 functions. We suggest that in genetically susceptible individuals, H. pylori infection can activate cross-reactive gastric T cells leading to gastric autoimmunity via molecular mimicry.