Requirements for autoimmune responses to mouse gastric autoantigens

Autoimmune gastritis, in which the H+/K+-ATPase of parietal cells is the major antigen, is one of the most common autoimmune diseases. Here we examined if specific properties of the H+/K+-ATPase or parietal cells are involved in rendering them autoimmune targets. The model antigens beta -galactosidase and ovalbumin (OVA) were expressed in parietal cells or transgenic mice. Oil experimental induction of autoimmune gastritis by neonatal thymectomy, autoantibodies to beta -galactosidase developed in mice expressing beta -galactosidase in parietal cells, a response that was independent of either the response to the gastric H+/K+-ATPase or gastric inflammation. In contrast, mice that expressed OVA in parietal cells did not exhibit all antibody response to OVA after thymectomy. However, increasing the frequency of anti-OVA T lymphocytes in OVA-expressing mice resulted in autoantibodies to OVA and gastritis. These Studies indicate that parietal cells can present a variety of antigens to the immune system. Factors such as the identity and expression level of the autoantigen and the frequency of autoreactive T cells play a role in determining the prevalence and outcome of the particular immune response. In addition, as not all mice of a particular genotype displayed autoimmunity, random events are involved in determining the target of autoimmune recognition.