Region of peptide 125-147 of acetylcholine receptor α subunit is exposed at neuromuscular junction and induces experimental autoimmune myasthenia gravis, T-cell immunity, and modulating autoantibodies

Vanda A Lennon, Daniel J Mc Cormick, E. H. Lambert, G. E. Griesmann, M. Z. Atassi

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Abstract

A major antigenic region of native nicotinic acetylcholine receptors (AcChoR) has been identified by using a synthetic disulfide-looped peptide corresponding to α-subunit residues 125-147 of Torpedo electric organ AcChoR: Lys-Ser-Tyr-Cys-Glu-Ile-Ile-Val-Thr-His-Phe-Pro-Phe-Asp-Gln-Gln-Asn-Cys-Th r-Met-Lys-Leu-Gly. The peptide bound 26-56% of polyclonal antibodies induced in rat, rabbit, and dog by immunization with native AcChoR. Rats inoculated with 50 μg of unconjugated peptide developed helper T-cell responses, delayed hypersensitivity, and antibodies to native AcChoR. Anti-peptide antibodies were more reactive with native than denatured AcChoR and bound to the α subunit. Some reacted exclusively with mammalian muscle AcChoR, some induced modulation of AcChoR on cultured myotubes, but none inhibited binding of α-bungarotoxin to solubilized or membrane-associated AcChoR. Repeated immunization induced experimental autoimmune myasthenia gravis: clinical signs in one rat and electrophysiologic and/or biochemical signs in 10 of 11 rats. Thus, at least part of the corresponding region of the mammalian AcChoR α subunit is extracellular at the neuromuscular junction and a potential target for pathogenic autoantibodies in patients with acquired myasthenia gravis.

Original languageEnglish (US)
Pages (from-to)8805-8809
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume82
Issue number24
StatePublished - 1985

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Autoimmune Experimental Myasthenia Gravis
Neuromuscular Junction
Cholinergic Receptors
Autoantibodies
Immunity
T-Lymphocytes
Peptides
Immunization
Electric Organ
Torpedo
Bungarotoxins
Antibodies
Myasthenia Gravis
Skeletal Muscle Fibers
Delayed Hypersensitivity
Nicotinic Receptors
Helper-Inducer T-Lymphocytes
Disulfides
Anti-Idiotypic Antibodies
Dogs

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

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title = "Region of peptide 125-147 of acetylcholine receptor α subunit is exposed at neuromuscular junction and induces experimental autoimmune myasthenia gravis, T-cell immunity, and modulating autoantibodies",
abstract = "A major antigenic region of native nicotinic acetylcholine receptors (AcChoR) has been identified by using a synthetic disulfide-looped peptide corresponding to α-subunit residues 125-147 of Torpedo electric organ AcChoR: Lys-Ser-Tyr-Cys-Glu-Ile-Ile-Val-Thr-His-Phe-Pro-Phe-Asp-Gln-Gln-Asn-Cys-Th r-Met-Lys-Leu-Gly. The peptide bound 26-56{\%} of polyclonal antibodies induced in rat, rabbit, and dog by immunization with native AcChoR. Rats inoculated with 50 μg of unconjugated peptide developed helper T-cell responses, delayed hypersensitivity, and antibodies to native AcChoR. Anti-peptide antibodies were more reactive with native than denatured AcChoR and bound to the α subunit. Some reacted exclusively with mammalian muscle AcChoR, some induced modulation of AcChoR on cultured myotubes, but none inhibited binding of α-bungarotoxin to solubilized or membrane-associated AcChoR. Repeated immunization induced experimental autoimmune myasthenia gravis: clinical signs in one rat and electrophysiologic and/or biochemical signs in 10 of 11 rats. Thus, at least part of the corresponding region of the mammalian AcChoR α subunit is extracellular at the neuromuscular junction and a potential target for pathogenic autoantibodies in patients with acquired myasthenia gravis.",
author = "Lennon, {Vanda A} and {Mc Cormick}, {Daniel J} and Lambert, {E. H.} and Griesmann, {G. E.} and Atassi, {M. Z.}",
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T1 - Region of peptide 125-147 of acetylcholine receptor α subunit is exposed at neuromuscular junction and induces experimental autoimmune myasthenia gravis, T-cell immunity, and modulating autoantibodies

AU - Lennon, Vanda A

AU - Mc Cormick, Daniel J

AU - Lambert, E. H.

AU - Griesmann, G. E.

AU - Atassi, M. Z.

PY - 1985

Y1 - 1985

N2 - A major antigenic region of native nicotinic acetylcholine receptors (AcChoR) has been identified by using a synthetic disulfide-looped peptide corresponding to α-subunit residues 125-147 of Torpedo electric organ AcChoR: Lys-Ser-Tyr-Cys-Glu-Ile-Ile-Val-Thr-His-Phe-Pro-Phe-Asp-Gln-Gln-Asn-Cys-Th r-Met-Lys-Leu-Gly. The peptide bound 26-56% of polyclonal antibodies induced in rat, rabbit, and dog by immunization with native AcChoR. Rats inoculated with 50 μg of unconjugated peptide developed helper T-cell responses, delayed hypersensitivity, and antibodies to native AcChoR. Anti-peptide antibodies were more reactive with native than denatured AcChoR and bound to the α subunit. Some reacted exclusively with mammalian muscle AcChoR, some induced modulation of AcChoR on cultured myotubes, but none inhibited binding of α-bungarotoxin to solubilized or membrane-associated AcChoR. Repeated immunization induced experimental autoimmune myasthenia gravis: clinical signs in one rat and electrophysiologic and/or biochemical signs in 10 of 11 rats. Thus, at least part of the corresponding region of the mammalian AcChoR α subunit is extracellular at the neuromuscular junction and a potential target for pathogenic autoantibodies in patients with acquired myasthenia gravis.

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