Myasthenia gravis (MG) is caused by helper T cell-dependent autoantibodies against the muscle acetylcholine receptor (AChR). Thymic epithelial tumors (thymomas) occur in 10% of MG patients, but their autoimmunizing potential is unclear. They express mRNAs encoding AChR ␣ and ⑀ subunits, and might aberrantly select or sensitize developing thymocytes or recirculating peripheral T cells against AChR epitopes. Alternatively, there could be defective selftolerance induction in the abundant maturing thymocytes that they usually generate. For the first time, we have isolated and characterized AChR-specific T cell clones from two MG thymomas. They recognize extracellular epitopes ( ␣ 75-90 and ␣ 149-158) which are processed very efficiently from muscle AChR. Both clones express CD4 and CD8 ␣ , and have a Th-0 cytokine profile, producing IL-4 as well as IFN-␥ . They are restricted to HLA-DP14 and DR52a; expression of these minority isotypes was strong on professional antigen-presenting cells in the donors' tumors, although it is generally weak in the periphery. The two clones' T cell receptor  chains are different, but their ␣ chain sequences are very similar. These resemblances, and the striking contrasts with T cells previously cloned from nonthymoma patients, show that thymomas generate and actively induce specific T cells rather than merely failing to tolerize them against self antigens. (
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