A conserved epitope on H+,K(+)-adenosine triphosphatase of parietal cells discerned by a murine gastritogenic T-cell clone.
OBJECTIVE
H+,K(+)-adenosine triphosphatase (H+,K(+)-ATPase) of parietal cells is an organ-specific enzyme recognized by autoantibodies found in human and murine autoimmune gastritis (AIG). Murine AIG can be induced in BALB/c mice by thymectomy 3 days after birth and is a T cell-mediated disease. This study examined the specificity of T cells that cause AIG and the role of H+,K(+)-ATPase in this disease.


METHODS
From an AIG mouse, a gastritogenic T-cell clone (II-6) was established, and its reactivity to synthetic peptides of H+,K(+)-ATPase was tested.


RESULTS
II-6 cells are CD4+, V beta 14+, and interferon gamma producers. Adoptive transfer of II-6 cells to syngeneic nude mice resulted in AIG without the production of autoantibodies to parietal cells. The II-6 cells were responsive not only to murine but also to human and porcine parietal cells. Their proliferation was also induced by amino acids 891-905 (alpha 891) and 892-906 (alpha 892) of the alpha subunit of porcine and human H+,K(+)-ATPase, respectively.


CONCLUSIONS
The T-cell response to a single epitope of H+,K(+)-ATPase, the amino acid sequence of which is conserved among at least three mammals tested, is sufficient to cause AIG. Autoantibodies to parietal cells are not detected in these AIG mice.
Nishio
A
A
First Department of Internal Medicine, Faculty of Medicine, Kyoto University, Japan.
Hosono
M
M
Watanabe
Y
Y
Sakai
M
M
Okuma
M
M
Masuda
T
T
D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000276:immunology; D001327:Autoimmune Diseases / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D002999:Clone Cells; D017124:Conserved Sequence; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D005756:Gastritis / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D017506:H(+)-K(+)-Exchanging ATPase / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008969:Molecular Sequence Data; D010295:Parietal Cells, Gastric / Q000201:enzymology* / Q000276:immunology; D013552:Swine; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology
D001324:Autoantigens; D000939:Epitopes; D017506:H(+)-K(+)-Exchanging ATPase