T helper cell recognition of muscle acetylcholine receptor in myasthenia gravis: Epitopes on the γ and δ subunits

We tested the response of CE4⁺ cells and/or total lymphocytes from the blood of 22 myasthenic patients and 10 healthy controls to overlapping synthetic peptides, 20 residues long, to screen the sequence of the γ and δ subunits of human muscle acetylcholine receptor (AChR). The γ subunit is part of the AChR expressed in embryonic muscle and is substituted in the AChRs of most adult muscles by an ε subunit. The δ subunit is present in both embryonic and adult AChRs. Adult extrinsic ocular muscles, which are preferentially and sometimes uniquely affected by myasthenic symptoms, and thymus, which has a still obscure but important role in the pathogenesis of myasthenia gravis, express the embryonic γ subunit. Anti-AChR CD4⁺ responses were more easily detected after CD8⁺ depletion. All responders recognized epitopes on both the γ and δ subunits and had severe symptoms. In four patients the CD4⁺ cell response was tested twice, when the symptoms were severe and during a period of remission. Consistently, the response was only detectable, or larger, when the patients were severely affected.