The Journal of Experimental Medicine
Rockland Immunochemicals for Research
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Published 20 October 2003. doi:10.1084/jem.20030530
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© Rockefeller University Press, 0022-1007/2003/10/1147 $5.00
The Journal of Experimental Medicine, Volume 198, Number 8, 1147-1156

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

Amedeo Amedei1, Mathijs P. Bergman2, Ben J. Appelmelk2, Annalisa Azzurri1, Marisa Benagiano1, Carlo Tamburini1, Ruurd van der Zee3, John L. Telford4, Christina M.J.E. Vandenbroucke-Grauls2, Mario M. D'Elios1 and Gianfranco Del Prete1

1 Department of Internal Medicine, University of Florence, 50134 Florence, Italy
2 Department of Medical Microbiology, Vrije Universiteit, Medical School, 1081 BT Amsterdam, Netherlands
3 Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, 3508 TD Utrecht, Netherlands
4 Chiron Vaccines, 53100 Siena, Italy

Address correspondence to Mario M. D'Elios, Dept. of Internal Medicine, Viale Morgagni 85, 50134 Florence, Italy. Phone: 39055-4296445; Fax: 39055-4271494; email: delios{at}unifi.it; or Gianfranco Del Prete, Phone: 39055-4378103; Fax: 39055-4378103; email: gdelprete{at}unifi.it

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.

Key Words: Helicobacter pylori • T cell epitopes • autoreactive T cells • mimicry • mucosal immunity


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