How promiscuity promotes tolerance: the case of myasthenia gravis.
Central T cell tolerance in the thymus plays a nonredundant role in preventing organ-specific autoimmunity. This role is largely attributable to promiscuous expression of tissue-restricted auto-antigens in medullary thymic epithelial cells (mTECs). The nascent T cell repertoire is exhaustively screened for potential autoreactivity against these ligands presented by mTECs. Failure of this screening process can result in organ-specific autoimmune diseases affecting single or multiple organs. Here we discuss how promiscuous expression of the acetylcholine receptor alpha-chain in the human thymus can potentially affect self-tolerance toward this well characterized auto-antigen and thus influence the disease course of myasthenia gravis.
Kyewski
Bruno
B
German Cancer Research Center, Developmental Immunology, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. b.kyewski@dkfz.de
Taubert
Richard
R
D015551:Autoimmunity / Q000276:immunology; D005786:Gene Expression Regulation; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D009157:Myasthenia Gravis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D009928:Organ Specificity; D011110:Polymorphism, Genetic / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000096927:AIRE Protein
D014157:Transcription Factors; D000096927:AIRE Protein