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 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.
Melms
A
A
Max-Planck-Gesellschaft, Clinical Research Unit for Multiple Sclerosis, Würzburg, Federal Republic of Germany.
Chrestel
S
S
Schalke
B C
BC
Wekerle
H
H
Mauron
A
A
Ballivet
M
M
Barkas
T
T
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D002478:Cells, Cultured; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology; D006239:Haplotypes; D006801:Humans; D008297:Male; D051379:Mice; D009157:Myasthenia Gravis / Q000276:immunology*; D011978:Receptors, Nicotinic / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014101:Torpedo
D000945:Antigens, Differentiation, T-Lymphocyte; D001324:Autoantigens; D000939:Epitopes; D006684:HLA-DR Antigens; D011978:Receptors, Nicotinic; D011994:Recombinant Proteins