T Helper Cell Recognition of Muscle Acetylcholine Receptor in Myasthenia Gravis Epitopes on the y and 5 Subunits

Wetested the response of CD4' 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 y and 5 subunits of human muscle acetylcholine receptor (AChR). The oy subunit is part of the AChRexpressed in embryonic muscle and is substituted in the AChRsof most adult muscles by an e subunit. The 5 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 'y subunit. AntiAChRCD4+ responses were more easily detected after CD8+ depletion. All responders recognized epitopes on both the y and a 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. (J. Clin. Invest. 1993. 92:1055-1067.)