How Promiscuity Promotes Tolerance: The Case of Myasthenia Gravis


*Present address: Dept. Gastroenterology, Hepatology and Endocrinology, Medical School Hannover, Hannover, Germany. Address for correspondence: Bruno Kyewski, German Cancer Research Center, Developmental Immunology, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. Tel.: +49-6221-423734; fax: +49-6221-423737.


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 α-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.