Shaping the T cell repertoire to a bona fide autoantigen: lessons from autoimmune gastritis
✍ Scribed by Ian R van Driel; Simon Read; Tricia D Zwar; Paul A Gleeson
- Publisher
- Elsevier Science
- Year
- 2005
- Tongue
- English
- Weight
- 215 KB
- Volume
- 17
- Category
- Article
- ISSN
- 0952-7915
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✦ Synopsis
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 alpha subunit is also expressed in the thymus, in an aire-independent manner, whereas the H(+)/K(+) ATPase beta 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.