Myasthenogenicity of human acetylcholine receptor synthetic α-subunit peptide 125-147 does not require intramolecular disulfide cyclization

D. J. McCormick, G. E. Griesmann, Z. X. Huang, E. H. Lambert, V. A. Lennon

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

This study reports the synthesis of a disulfide-looped peptide corresponding to residues 125-147 (Cys 128-Cys 142) of the nicotinic acetylcholine receptor (AChR) of human skeletal muscle, Hα125-147 (Lys-Ser-Tyr-Cys-Glu-Ile-Ile-Val-Thr-His-Phe-Pro-Phe-Asp-Glu -Gln-Asn-Cys-Ser-Nle-Lys-Leu-Gly), and a nondisulfide-looped analogue, Hα125-147(S) (Lys-Ser-Tyr-Ser-Glu-Ile-Ile-Val-Thr-His-Phe-Pro-Phe-Asp-Glu -Gln-Asn-Cys-Ser-Nle-Lys-Leu-Gly), in which the amino acid Cys 128 was replaced with serine. Both peptides induced antigen-specific helper T cell responses, as evidenced in vitro by lymph node cell proliferation and in vivo by production of anti-AChR antibodies. Rats immunized with 100 μg of either synthetic peptide, without conjugation to a carrier, produced anti-peptide antibodies which bound to native AChR in immunoprecipitation assays and induced modulation of membrane-bound AChR from cultured human myotubes. Both peptides also induced electrophysiologic and biochemical signs of experimental autoimmune myasthenia gravis. Thus, region 125-147 of the AchR α-subunit is at least partly exposed extracellularly in human muscle and contains one or more autoantigenic sites capable of stimulating T cells and B cells. Disulfide-linkage between residues Cys 128 and Cys 142 is not essential for myasthenogenicity.

Original languageEnglish (US)
Pages (from-to)2615-2619
Number of pages5
JournalJournal of Immunology
Volume139
Issue number8
StatePublished - Dec 1 1987

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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