Autoimmune T Lymphocytes in ' Myasthenia Gravis Determination of Target Epitopes Using T Lines and Recombinant Products of the Mouse Nicotinic Acetylcholine Receptor Gene

Oligoclonal and cloned T lines from peripheral blood or thy-muses of patients with myasthenia gravis (MG) were selected for reactivity against nicotinic acetylcholine receptors (AChR) from Torpedo californica, or against a recombinant fusion peptide, X4, representing the extracellular portion of the mouse AChR a-chain. All cell lines expressed the CD4 mem-brane phenotype, and their antigen reactivity was blocked by antibodies against monomorphic HLA DR/DP determinants. Using a panel of fusion proteins of different, overlapping mouse AChR a-chain sequences, a major T cell epitope was localized between amino acid positions 85 and 142. This deter-minant was distinct from the humoral main immunogenic re-gion, which has been identified on the sequence 61-76. The response pattern of uncloned T lines from three pa-tients with different HLA haplotypes suggests, however, that in any one MG patient T lymphocytes may recognize more than one autoantigenic epitope on the AChR a-chain, and that the T lymphocyte response profiles vary among individual pa-tients