Requirements for autoimmune responses to mouse gastric autoantigens

Autoimmune gastritis, in which the H+/K+-ATPase of parietal cells is the ma jor antigen, is one of the most common autoimmune diseases. Here we examine d if specific properties of the H+/K+-ATPase or parietal cells are involved in rendering them autoimmune targets. The model antigens beta -galactosida se 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 -g alactosidase in parietal cells, a response that was independent of either t he response to the gastric H+/K+-ATPase or gastric inflammation. In contras t, mice that expressed OVA in parietal cells did not exhibit all antibody r esponse 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 var iety of antigens to the immune system. Factors such as the identity and exp ression level of the autoantigen and the frequency of autoreactive T cells play a role in determining the prevalence and outcome of the particular imm une response. In addition, as not all mice of a particular genotype display ed autoimmunity, random events are involved in determining the target of au toimmune recognition.