Definition of myasthenogenic sites of the human acetylcholine receptor using synthetic peptides

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

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Experimental autoimmune myasthenia gravis (EAMG) and antibodies that modulate AChRs from cultured human muscle are induced by a disulfide-looped peptide comprising the human acetylcholine receptor (AChR) α-subunit residues 125-147 (Hα125-147). To delineate the essential antigenic requirements for induction of EAMG by this peptide, a series of peptides was synthesized: (a) a nonlooped analog (Cys 128 replaced by Ser) stimulated modulating autoantibodies, induced EAMG, and bound antibodies induced by native AChR; (b) Hα131-147, a heptadecylpeptide shorter by 6 N-terminal residues, induced modulating antibodies, EAMG, and T cells that responded to Hα125-147, but not to Hα137-147; (c) Hα137-147, an undecapeptide shorter than Hα125-147 by 12 N-terminal residues, did not stimulate T cells or induce antibody production, but it bound antibodies generated by the longer peptides. Thus, when coupled to an epitope that could stimulate helper T cells, the region 137-147 was able to stimulate B cells. This study has defined a myasthenogenic region of the human AChR's α-subunit, 17 amino acids long, that contains several distinct epitopes, including at least one N-terminal site inducing T-cell responses (region 131-136) and two possibly overlapping sites that induce antibodies (regions 131-136 and 137-147). Further definition of antigenic sites inducing helper and suppressor T-cell responses and stimulating production of autoantibodies to AChR is essential to the goal of antigen-specific immunotherapy for myasthenia gravis.

Original languageEnglish (US)
Pages (from-to)439-450
Number of pages12
JournalAnnals of the New York Academy of Sciences
Volume505
StatePublished - 1987

Fingerprint

Autoimmune Experimental Myasthenia Gravis
Cholinergic Receptors
T-cells
Peptides
Antibodies
Helper-Inducer T-Lymphocytes
T-Lymphocytes
Autoantibodies
Epitopes
Myasthenia Gravis
Disulfides
Immunotherapy
Antibody Formation
B-Lymphocytes
Muscle
Cells
Antigens
Amino Acids
Muscles

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Definition of myasthenogenic sites of the human acetylcholine receptor using synthetic peptides. / Lennon, Vanda A; Griesmann, G. A.; Mc Cormick, Daniel J; Huang, Z. X.; Feng, H.; Lambert, E. H.

In: Annals of the New York Academy of Sciences, Vol. 505, 1987, p. 439-450.

Research output: Contribution to journalArticle

@article{fbb3261512f24a019e8f1fb096d4c0cc,
title = "Definition of myasthenogenic sites of the human acetylcholine receptor using synthetic peptides",
abstract = "Experimental autoimmune myasthenia gravis (EAMG) and antibodies that modulate AChRs from cultured human muscle are induced by a disulfide-looped peptide comprising the human acetylcholine receptor (AChR) α-subunit residues 125-147 (Hα125-147). To delineate the essential antigenic requirements for induction of EAMG by this peptide, a series of peptides was synthesized: (a) a nonlooped analog (Cys 128 replaced by Ser) stimulated modulating autoantibodies, induced EAMG, and bound antibodies induced by native AChR; (b) Hα131-147, a heptadecylpeptide shorter by 6 N-terminal residues, induced modulating antibodies, EAMG, and T cells that responded to Hα125-147, but not to Hα137-147; (c) Hα137-147, an undecapeptide shorter than Hα125-147 by 12 N-terminal residues, did not stimulate T cells or induce antibody production, but it bound antibodies generated by the longer peptides. Thus, when coupled to an epitope that could stimulate helper T cells, the region 137-147 was able to stimulate B cells. This study has defined a myasthenogenic region of the human AChR's α-subunit, 17 amino acids long, that contains several distinct epitopes, including at least one N-terminal site inducing T-cell responses (region 131-136) and two possibly overlapping sites that induce antibodies (regions 131-136 and 137-147). Further definition of antigenic sites inducing helper and suppressor T-cell responses and stimulating production of autoantibodies to AChR is essential to the goal of antigen-specific immunotherapy for myasthenia gravis.",
author = "Lennon, {Vanda A} and Griesmann, {G. A.} and {Mc Cormick}, {Daniel J} and Huang, {Z. X.} and H. Feng and Lambert, {E. H.}",
year = "1987",
language = "English (US)",
volume = "505",
pages = "439--450",
journal = "Annals of the New York Academy of Sciences",
issn = "0077-8923",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Definition of myasthenogenic sites of the human acetylcholine receptor using synthetic peptides

AU - Lennon, Vanda A

AU - Griesmann, G. A.

AU - Mc Cormick, Daniel J

AU - Huang, Z. X.

AU - Feng, H.

AU - Lambert, E. H.

PY - 1987

Y1 - 1987

N2 - Experimental autoimmune myasthenia gravis (EAMG) and antibodies that modulate AChRs from cultured human muscle are induced by a disulfide-looped peptide comprising the human acetylcholine receptor (AChR) α-subunit residues 125-147 (Hα125-147). To delineate the essential antigenic requirements for induction of EAMG by this peptide, a series of peptides was synthesized: (a) a nonlooped analog (Cys 128 replaced by Ser) stimulated modulating autoantibodies, induced EAMG, and bound antibodies induced by native AChR; (b) Hα131-147, a heptadecylpeptide shorter by 6 N-terminal residues, induced modulating antibodies, EAMG, and T cells that responded to Hα125-147, but not to Hα137-147; (c) Hα137-147, an undecapeptide shorter than Hα125-147 by 12 N-terminal residues, did not stimulate T cells or induce antibody production, but it bound antibodies generated by the longer peptides. Thus, when coupled to an epitope that could stimulate helper T cells, the region 137-147 was able to stimulate B cells. This study has defined a myasthenogenic region of the human AChR's α-subunit, 17 amino acids long, that contains several distinct epitopes, including at least one N-terminal site inducing T-cell responses (region 131-136) and two possibly overlapping sites that induce antibodies (regions 131-136 and 137-147). Further definition of antigenic sites inducing helper and suppressor T-cell responses and stimulating production of autoantibodies to AChR is essential to the goal of antigen-specific immunotherapy for myasthenia gravis.

AB - Experimental autoimmune myasthenia gravis (EAMG) and antibodies that modulate AChRs from cultured human muscle are induced by a disulfide-looped peptide comprising the human acetylcholine receptor (AChR) α-subunit residues 125-147 (Hα125-147). To delineate the essential antigenic requirements for induction of EAMG by this peptide, a series of peptides was synthesized: (a) a nonlooped analog (Cys 128 replaced by Ser) stimulated modulating autoantibodies, induced EAMG, and bound antibodies induced by native AChR; (b) Hα131-147, a heptadecylpeptide shorter by 6 N-terminal residues, induced modulating antibodies, EAMG, and T cells that responded to Hα125-147, but not to Hα137-147; (c) Hα137-147, an undecapeptide shorter than Hα125-147 by 12 N-terminal residues, did not stimulate T cells or induce antibody production, but it bound antibodies generated by the longer peptides. Thus, when coupled to an epitope that could stimulate helper T cells, the region 137-147 was able to stimulate B cells. This study has defined a myasthenogenic region of the human AChR's α-subunit, 17 amino acids long, that contains several distinct epitopes, including at least one N-terminal site inducing T-cell responses (region 131-136) and two possibly overlapping sites that induce antibodies (regions 131-136 and 137-147). Further definition of antigenic sites inducing helper and suppressor T-cell responses and stimulating production of autoantibodies to AChR is essential to the goal of antigen-specific immunotherapy for myasthenia gravis.

UR - http://www.scopus.com/inward/record.url?scp=0023614632&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023614632&partnerID=8YFLogxK

M3 - Article

C2 - 2446556

AN - SCOPUS:0023614632

VL - 505

SP - 439

EP - 450

JO - Annals of the New York Academy of Sciences

JF - Annals of the New York Academy of Sciences

SN - 0077-8923

ER -