Assuntos
Doenças Autoimunes/imunologia , Miastenia Gravis/imunologia , Receptores Nicotínicos/imunologia , Acetilcolina/metabolismo , Animais , Autoanticorpos/imunologia , Autoanticorpos/metabolismo , Bungarotoxinas/metabolismo , Terapia Combinada , Modelos Animais de Doenças , Epitopos/imunologia , Humanos , Imunidade Celular , Ativação do Canal Iônico , Modelos Biológicos , Miastenia Gravis/terapia , Junção Neuromuscular/fisiopatologia , Coelhos , Receptores Colinérgicos/imunologia , Receptores Colinérgicos/metabolismo , Receptores Nicotínicos/metabolismo , Relação Estrutura-Atividade , Linfócitos T Citotóxicos/imunologia , Timo/fisiopatologia , Torpedo/imunologia , Torpedo/metabolismo , Receptor Nicotínico de Acetilcolina alfa7RESUMO
Oligoclonal and cloned T lines from peripheral blood or thymuses of patients with myasthenia gravis (MG) were selected for reactivity against nicotinic acetylcholine receptors (AChR) from Torpedo california, or against a recombinant fusion peptide, X4, representing the extracellular portion of the mouse AChR alpha-chain. All cell lines expressed the CD4 membrane 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 alpha-chain sequences, a major T cell epitope was localized between amino acid positions 85 and 142. This determinant was distinct from the humoral main immunogenic region, which has been identified on the sequence 61-76. The response pattern of uncloned T lines from three patients with different HLA haplotypes suggests, however, that in any one MG patient T lymphocytes may recognize more than one autoantigenic epitope on the AChR alpha-chain, and that the T lymphocyte response profiles vary among individual patients.
