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.