EXPRESSION OF THE GASTRIC H K-ATPASE ALPHA-SUBUNIT IN THE THYMUS MAY EXPLAIN THE DOMINANT ROLE OF THE BETA-SUBUNIT IN THE PATHOGENESIS OF AUTOIMMUNE GASTRITIS/

The two subunits of the gastric H/K ATPase, namely the catalytic alpha -subunit and the glycoprotein beta-subunit, are the major targets of p arietal cell autoantibodies associated with human and murine autoimmun e gastritis, The murine disease induced by neonatal thymectomy is T ce ll-mediated, We have previously shown that transgenic expression of th e H/K ATPase beta-subunit gene in the thymus prevented the development of autoimmune gastritis induced by thymectomy, However, little is kno wn of the contribution of the H/K ATPase alpha-subunit in disease deve lopment, Here, we show that (1) in contrast to the gastric H/K ATPase beta-subunit, the alpha-subunit gene is expressed in normal BALB/c thy mus, (2) transgenic expression of the gastric H/K ATPase alpha-subunit gene in the thymus failed to prevent the development of autoimmune ga stritis and (3) normal BALB/c and transgenic mice expressing the alpha -subunit in the thymus develop autoimmune gastritis following immunisa tion with purified murine gastric H/K ATPase, whereas transgenic mice expressing the beta-subunit in the thymus do not, We propose that the expression of the H/K ATPase alpha-subunit in the normal thymus ma!: a ccount for the predominant role of the beta-subunit in the development of autoimmune gastritis induced either by thymectomy or by immunisati on with the ATPase.