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

Angelo A. Manfredi, Maria Pia Protti, Mark W M Dalton, James F. Howard, Bianca M. Conti-Tronconi

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)1055-1067
Number of pages13
JournalJournal of Clinical Investigation
Volume92
Issue number2
Publication statusPublished - Aug 1993

Keywords

  • Autoimmunity
  • Embryonic acetylcholine receptor
  • T epitopes

ASJC Scopus subject areas

  • Medicine(all)

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