Molecular mimicry between Helicobacter pylori antigens and H+, K+ --adenosine triphosphatase in human gastric autoimmunity

• Published in: The Journal of experimental medicine Vol. 198; no. 8; pp. 1147 - 1156
• Main Authors: Amedei, Amedeo, Bergman, Mathijs P, Appelmelk, Ben J, Azzurri, Annalisa, Benagiano, Marisa, Tamburini, Carlo, van der Zee, Ruurd, Telford, John L, Vandenbroucke-Grauls, Christina M J E, D'Elios, Mario M, Del Prete, Gianfranco
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 20-10-2003
• Subjects: Adult; Antigens, Bacterial - immunology; Autoantigens - immunology; Autoimmune Diseases - microbiology; Cross Reactions; Epitopes, T-Lymphocyte - immunology; Female; Gastric Mucosa - immunology; Gastritis, Atrophic - immunology; Gastritis, Atrophic - microbiology; H(+)-K(+)-Exchanging ATPase - immunology; Helicobacter Infections - immunology; Helicobacter pylori - immunology; HLA-DQ Antigens - immunology; HLA-DR Antigens - immunology; Humans; Lymphocyte Activation; Middle Aged; Molecular Mimicry; Stomach - immunology; T-Lymphocytes - immunology
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.20030530

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.