Autoimmune human T lymphocytes specific for acetylcholine receptor

Abstract

Myasthenia gravis is one of the best characterized human autoimmune disorders. Circulating autoantibodies to the nicotinic acetylcholine receptor (AChR) at the neuromuscular junction play a prominent part in the effector phase, that is, the immunoregulation. Indirect evidence, such as thymic abnormalities and the association with certain histocompatibility antigens (for example HLA-B8,-DR3) suggests a defect of immunoregulation at the level of thymus-dependent (T) lymphocytes. We report here on the isolation of autoreactive T cells from six patients with myasthenia gravis. From one of these patients, who is homozygous for HLA-DR3, we established a long-term T-cell line. The line cells are specific for purified fish and human AChR, display the surface phenotype of inducer/helper T cells and are genetically restricted to HLA-DR3. AChR-induced proliferation could be inhibited with two monoclonal antibodies against monomorphic DR determinants and also with DR3-specific alloantiserum.