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PMID: 2461962 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

In vitro proliferative responses and antibody titers specific to human acetylcholine receptor synthetic peptides in patients with myasthenia gravis and relation to HLA class II genes.

The Journal of clinical investigation ·Vol. 82 ·No. 6 ·1988-12-00 ·Pages 1894-900

Brocke S, Brautbar C, Steinman L, Abramsky O, Rothbard J, Neumann D, Fuchs S, Mozes E

Abstract

To investigate which parts of the acetylcholine receptor are involved in the initiation and development of myasthenia gravis (MG), peptides representing different sequences of the human acetylcholine receptor alpha-subunit were synthesized. These peptides were tested for their ability to stimulate T cells of myasthenic patients and healthy control patients in proliferation assays and to bind to sera antibodies. Three of eight peptides discriminated significantly between the two groups in the proliferation assay, as well as in their ability to bind to serum antibodies. HLA-DR3 and DR5 were associated with proliferative responses to specific AChR peptides in the group of myasthenics. Acetylcholine receptor epitopes that might play a specific role in myasthenia gravis thus were demonstrated.

MeSH Terms
Amino Acid Sequence Cell Division/drug effects Epitopes/analysis,immunology Genes, MHC Class II HLA-D Antigens/genetics HLA-DR Antigens/genetics HLA-DR3 Antigen HLA-DR5 Antigen Humans Macromolecular Substances Molecular Sequence Data Myasthenia Gravis/immunology Receptors, Cholinergic/chemical synthesis,immunology
Chemicals
Epitopes HLA-D Antigens HLA-DR Antigens HLA-DR3 Antigen HLA-DR5 Antigen Macromolecular Substances Receptors, Cholinergic
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Brocke S
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
Brautbar C
Steinman L
Abramsky O
Rothbard J
Neumann D
Fuchs S
Mozes E
References (29)
29 references, click to expand
  1. Serotyping for homotransplantation. 18. Refinement of microdroplet lymphocyte cytotoxicity test.
    Transplantation. 1968 Nov;6(8):913-27 PMID: 5696820
  2. A sequence pattern common to T cell epitopes.
    EMBO J. 1988 Jan;7(1):93-100 PMID: 2452085
  3. Microdroplet testing for HLA-A, -B, -C, and -D antigens. The Phillip Levine Award Lecture.
    Am J Clin Pathol. 1978 Feb;69(2):103-20 PMID: 75690
  4. Significance in neonatal myasthenia gravis of inhibitory effect of amniotic fluid on binding of antibodies to acetylcholine receptor.
    Lancet. 1979 Dec 22-29;2(8156-8157):1333-5 PMID: 92675
  5. Clinical, pathological, HLA antigen and immunological evidence for disease heterogeneity in myasthenia gravis.
    Brain. 1980 Sep;103(3):579-601 PMID: 6968236
  6. Immune response potential to poly(Tyr,Glu)-poly(DLAla)--poly(Lys) of human T cells of different donors.
    Proc Natl Acad Sci U S A. 1981 Jul;78(7):4505-9 PMID: 6170066
  7. HLA-D typing in multiple sclerosis: Israelis tested with European homozygous typing cells.
    Tissue Antigens. 1982 Mar;19(3):189-97 PMID: 6953617
  8. Anti-acetylcholine receptor antibodies in myasthenia gravis. Part 1. Relation to clinical parameters in 250 patients.
    J Neurol Sci. 1983 Mar;58(3):357-70 PMID: 6842264
  9. In vivo therapy with monoclonal anti-I-A antibody suppresses immune responses to acetylcholine receptor.
    Proc Natl Acad Sci U S A. 1983 May;80(9):2713-7 PMID: 6405386
  10. Cellular response to human acetylcholine receptor in patients with myasthenia gravis.
    J Neuroimmunol. 1983 Aug;5(1):59-65 PMID: 6603473
  11. Autoimmune human T lymphocytes specific for acetylcholine receptor.
    Nature. 1984 Jul 19-25;310(5974):244-6 PMID: 6611507
  12. Sharing of antigenic determinants between the nicotinic acetylcholine receptor and proteins in Escherichia coli, Proteus vulgaris, and Klebsiella pneumoniae. Possible role in the pathogenesis of myasthenia gravis.
    N Engl J Med. 1985 Jan 24;312(4):221-5 PMID: 2578213
  13. Mutation at I-A beta chain prevents experimental autoimmune myasthenia gravis.
    Immunogenetics. 1985;21(1):33-8 PMID: 3917973
  14. Antibodies to synthetic peptides as probes for the binding site on the alpha subunit of the acetylcholine receptor.
    Proc Natl Acad Sci U S A. 1985 May;82(10):3490-3 PMID: 2582416
  15. (T,G)-A-L specific immune response potential and HLA typing of Israeli patients with systemic lupus erythematosus.
    Clin Exp Immunol. 1985 May;60(2):355-62 PMID: 2408803
  16. Binding of immunogenic peptides to Ia histocompatibility molecules.
    Nature. 1985 Sep 26-Oct 2;317(6035):359-61 PMID: 3876513
  17. Immunobiology of myasthenia gravis, experimental autoimmune myasthenia gravis, and Lambert-Eaton syndrome.
    Annu Rev Immunol. 1985;3:109-31 PMID: 2998417
  18. Determination of the primary amino acid sequence specifying the alpha-bungarotoxin binding site on the alpha subunit of the acetylcholine receptor from Torpedo californica.
    Proc Natl Acad Sci U S A. 1985 Dec;82(24):8790-4 PMID: 3866252
  19. Localization of a highly immunogenic region on the acetylcholine receptor alpha-subunit.
    Biochem Biophys Res Commun. 1986 Feb 26;135(1):82-9 PMID: 2420332
  20. HLA-DQ beta-chain polymorphism linked to myasthenia gravis.
    Lancet. 1986 May 10;1(8489):1058-60 PMID: 2871336
  21. Mapping of the alpha-bungarotoxin binding site within the alpha subunit of the acetylcholine receptor.
    Proc Natl Acad Sci U S A. 1986 May;83(9):3008-11 PMID: 3458258
  22. Analysis of the biological functions and fine specificity of (T,G)-A--L specific T cell clones.
    Immunobiology. 1986 Aug;172(1-2):99-109 PMID: 2429916
  23. T-cell epitope of the autoantigen myelin basic protein that induces encephalomyelitis.
    Nature. 1986 Nov 20-26;324(6094):258-60 PMID: 2431317
  24. Localization of the functional sites on the alpha chain of acetylcholine receptor.
    Fed Proc. 1987 Jun;46(8):2538-47 PMID: 2439384
  25. A molecular basis for MHC class II--associated autoimmunity.
    Science. 1988 May 20;240(4855):1003-9 PMID: 3368786
  26. Myasthenogenicity of human acetylcholine receptor synthetic alpha-subunit peptide 125-147 does not require intramolecular disulfide cyclization.
    J Immunol. 1987 Oct 15;139(8):2615-9 PMID: 3498765
  27. Amphipathic segment of the nicotinic receptor alpha subunit contains epitopes recognized by T lymphocytes in myasthenia gravis.
    J Clin Invest. 1988 Mar;81(3):657-60 PMID: 2449458
  28. Analysis of the antigen specific helper T cell function and HLA-DR of Israeli patients with rheumatoid arthritis (RA).
    Tissue Antigens. 1987 Nov;30(5):229-34 PMID: 2964098
  29. Antibody to acetylcholine receptor in myasthenia gravis. Prevalence, clinical correlates, and diagnostic value.
    Neurology. 1976 Nov;26(11):1054-9 PMID: 988512
Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
Published
1988-12-00
Pages
1894-900
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC442769
Subset
IM
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