Acetylcholine receptor-specific T-lymphocyte clones in the normal human immune repertoire: target epitopes, HLA restriction, and membrane phenotypes.
Potentially autoimmune T-lymphocyte lines specific for the nicotinic acetylcholine receptor of the neuromuscular junction have been isolated previously from patients with myasthenia gravis. We report on the isolation and expansion of T cells specific for the acetylcholine receptor of Torpedo californica or for a recombinant mammalian acetylcholine receptor alpha chain peptide (X4), from the peripheral blood of 11 healthy donors. Two major T-cell epitopes, located between amino acid positions 44-104 and 141-172, were identified using a panel of overlapping mammalian alpha chain fusion proteins. Most T lines recognized the acetylcholine receptor epitopes in the molecular context of HLA-DR molecules. Unexpectedly, all the T. californica acetylcholine receptor-specific T lines obtained from one DR4 (DRw53), DQw3 donor and two DR4, w8 (DRw53), DQw3 donors were restricted by DRw53 product(s). Using DR gene-transfected L cells as antigen presenters, in 4 lines, a close relationship between the recognized epitope and the restricting DR element was revealed. The membrane phenotype of the T. californica acetylcholine receptor-and X4-specific T lines was predominantly CD4+CD8-, with some CD4+CD8+ components. It did not significantly differ from that of control, tuberculin purified protein derivate-specific T lines raised from the same donors. These findings are in harmony with previous ones demonstrating the presence of potentially autoimmune T-lymphocyte clones within normal immune repertoires.
Salvetti
M
M
Max-Planck-Society, Clinical Research Unit for Multiple Sclerosis, Würzburg, Federal Republic of Germany.
Jung
S
S
Chang
S F
SF
Will
H
H
Schalke
B C
BC
Wekerle
H
H
D015703:Antigens, CD / Q000032:analysis; D002462:Cell Membrane / Q000276:immunology; D002999:Clone Cells; D000939:Epitopes / Q000276:immunology; D006680:HLA Antigens / Q000032:analysis; D006801:Humans; D008285:Major Histocompatibility Complex / Q000276:immunology; D010641:Phenotype; D011950:Receptors, Cholinergic / Q000276:immunology*; D012016:Reference Values; D015183:Restriction Mapping; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D000939:Epitopes; D006680:HLA Antigens; D011950:Receptors, Cholinergic