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 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.
van Driel
Ian R
IR
The Department of Biochemistry and Molecular Biology and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Victoria 3010, Australia.
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Simon
S
Zwar
Tricia D
TD
Gleeson
Paul A
PA
D000818:Animals; D017951:Antigen Presentation; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology* / Q000382:microbiology; D005756:Gastritis / Q000276:immunology* / Q000382:microbiology; D017506:H(+)-K(+)-Exchanging ATPase / Q000235:genetics / Q000276:immunology*; D016481:Helicobacter Infections / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D017634:Self Tolerance; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology
D001324:Autoantigens; D017506:H(+)-K(+)-Exchanging ATPase