A CONSERVED EPITOPE ON H+,K+-ADENOSINE TRIPHOSPHATASE OF PARIETAL-CELLS DISCERNED BY A MURINE GASTRITOGENIC T-CELL CLONE

Background/Aims: 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+-Pase, 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.