Shaping the T cell repertoire to a bona fide autoantigen: lessons from autoimmune gastritis

Murine autoimmune gastritis is one of the most well-defined organ-specific autoimmune diseases. CD4+ T cells, which mediate the disease, recognize the highly abundant gastric H+/K+ ATPase heterodimer. The H+/K+ ATPase α subunit is also expressed in the thymus, in an aire-independent manner, whereas the H+/K+ ATPase β subunit is absent from the thymus. Analysis of both H+/K+ ATPase-specific T cell receptor transgenic mice with different affinities for the gastric antigen and mice deficient in the H+/K+ ATPase subunits has provided information on thymic and peripheral selection events. The H+/K+ ATPase antigens play an important role in purging the repertoire of gastritogenic T cells, and recent data have suggested that this tolerance induction occurs primarily in the periphery. The gastritis system provides a powerful approach to determine the impact of peripheral antigen presentation in the target organ draining lymph node on tolerance and autoimmune disease.