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

Daniel J Mc Cormick, G. E. Griesmann, Z. X. Huang, E. H. Lambert, Vanda A Lennon

Research output: Contribution to journalArticle

27 Citations (Scopus)

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 - 1987

Fingerprint

Cholinergic Receptors
Cyclization
Disulfides
Peptides
Autoimmune Experimental Myasthenia Gravis
Skeletal Muscle Fibers
Nicotinic Receptors
Helper-Inducer T-Lymphocytes
Immunoprecipitation
Serine
Anti-Idiotypic Antibodies
Skeletal Muscle
B-Lymphocytes
Lymph Nodes
Cell Proliferation
T-Lymphocytes
Antigens
Amino Acids
Muscles
Membranes

ASJC Scopus subject areas

  • Immunology

Cite this

Myasthenogenicity of human acetylcholine receptor synthetic α-subunit peptide 125-147 does not require intramolecular disulfide cyclization. / Mc Cormick, Daniel J; Griesmann, G. E.; Huang, Z. X.; Lambert, E. H.; Lennon, Vanda A.

In: Journal of Immunology, Vol. 139, No. 8, 1987, p. 2615-2619.

Research output: Contribution to journalArticle

@article{93d45295b08945f386aa59e15ddd3108,
title = "Myasthenogenicity of human acetylcholine receptor synthetic α-subunit peptide 125-147 does not require intramolecular disulfide cyclization",
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.",
author = "{Mc Cormick}, {Daniel J} and Griesmann, {G. E.} and Huang, {Z. X.} and Lambert, {E. H.} and Lennon, {Vanda A}",
year = "1987",
language = "English (US)",
volume = "139",
pages = "2615--2619",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "8",

}

TY - JOUR

T1 - Myasthenogenicity of human acetylcholine receptor synthetic α-subunit peptide 125-147 does not require intramolecular disulfide cyclization

AU - Mc Cormick, Daniel J

AU - Griesmann, G. E.

AU - Huang, Z. X.

AU - Lambert, E. H.

AU - Lennon, Vanda A

PY - 1987

Y1 - 1987

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0023637254&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023637254&partnerID=8YFLogxK

M3 - Article

C2 - 3498765

AN - SCOPUS:0023637254

VL - 139

SP - 2615

EP - 2619

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 8

ER -