Expression of the Gastric H/K-ATPase α-Subunit in the Thymus may Explain the Dominant Role of the β-Subunit in the Pathogenesis of Autoimmune Gastritis

Abstract

The two subunits of the gastric H/K ATPase, namely the catalytic α-subunit and the glycoprotein β-subunit, are the major targets of parietal cell autoantibodies associated with human and murine autoimmune gastritis. The murine disease induced by neonatal thymectomy is T cell-mediated. We have previously shown that transgenic expression of the H/K ATPase β-subunit gene in the thymus prevented the development of autoimmune gastritis induced by thymectomy. However, little is known of the contribution of the H/K ATPase α-subunit in disease development. Here, we show that (1) in contrast to the gastric H/K ATPase β-subunit, the α-subunit gene is expressed in normal BALB/c thymus, (2) transgenic expression of the gastric H/K ATPase α-subunit gene in the thymus failed to prevent the development of autoimmune gastritis and (3) normal BALB/c and transgenic mice expressing the α-subunit in the thymus develop autoimmune gastritis following immunisation with purified murine gastric H/K ATPase, whereas transgenic mice expressing the β-subunit in the thymus do not. We propose that the expression of the H/K ATPase α-subunit in the normal thymus may account for the predominant role of the β-subunit in the development of autoimmune gastritis induced either by thymectomy or by immunisation with the ATPase.

Key Words:

• Thymus
• Autoantigen
• Transgenic
• Autoimmune gastritis
• H/K ATPase