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.
Department of Internal Medicine, Viale Morgagni 85, 50134 Florence, Italy.
Amedeo
A
Amedei
Mathijs P
MP
Bergman
Ben J
BJ
Appelmelk
Annalisa
A
Azzurri
Marisa
M
Benagiano
Carlo
C
Tamburini
Ruurd
R
van der Zee
John L
JL
Telford
Christina M J E
CM
Vandenbroucke-Grauls
Mario M
MM
D'Elios
Gianfranco
G
Del Prete
D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000382:microbiology*; D003429:Cross Reactions; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D005753:Gastric Mucosa / Q000276:immunology; D005757:Gastritis, Atrophic / Q000276:immunology* / Q000382:microbiology; D017506:H(+)-K(+)-Exchanging ATPase / Q000276:immunology*; D006683:HLA-DQ Antigens / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology; D016481:Helicobacter Infections / Q000276:immunology; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D008875:Middle Aged; D018716:Molecular Mimicry; D013270:Stomach / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D000942:Antigens, Bacterial; D001324:Autoantigens; D018984:Epitopes, T-Lymphocyte; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D017506:H(+)-K(+)-Exchanging ATPase