Monoclonal Antibodies Used to Probe Acetylcholine Receptor Structure: Localization of the Main Immunogenic Region and Detection of Similarities Between Subunits

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1980 Feb 1

PMID 6153804

Citations 97

Authors

S J Tzartos

J M Lindstrom

Affiliations

Soon will be listed here.

Abstract

Seventeen cell lines producing monoclonal antibodies against Torpedo californica (torpedo) acetylcholine receptor (AcChoR) and its subunits were established. By using these antibodies as probes, we identified: (i) a similar antigenic determinant on alpha and beta torpedo subunits, (ii) a similar antigenic determinant on gamma and delta subunits, (iii) antigenic determinants unique for alpha or beta torpedo AcChoR subunits, (iv) a small region on the alpha subunit that dominates the immunogenicity of native torpedo AcChoR in rats (a monoclonal antibody directed at this region could bind to rat AcChoR in vivo and cause passive experimental autoimmune myasthenia gravis), and (v) antigenic determinants on torpedo subunits recognized in AcChoR from other species. The unexpected similarities between alpha and beta and between gamma and delta subunits raise the possibility that the complex four-subunit structure of AcChoR was derived from a simpler precursor and suggests that these antigenic similarities might reflect some structural and functional homologies.

Citing Articles

Development of Peptide Mimics of the Human Acetylcholine Receptor Main Immunogenic Region for Treating Myasthenia Gravis.

Trinh V, Fairclough R Int J Mol Sci. 2025; 26(1.

PMID: 39796084 PMC: 11719904. DOI: 10.3390/ijms26010229.

Functional Signature of LRP4 Antibodies in Myasthenia Gravis.

Chuquisana O, Stascheit F, Keller C, Pucic-Bakovic M, Patenaude A, Lauc G Neurol Neuroimmunol Neuroinflamm. 2024; 11(3):e200220.

PMID: 38507656 PMC: 10959168. DOI: 10.1212/NXI.0000000000200220.

Modulation of a rapid neurotransmitter receptor-ion channel by membrane lipids.

Barrantes F Front Cell Dev Biol. 2024; 11:1328875.

PMID: 38274273 PMC: 10808158. DOI: 10.3389/fcell.2023.1328875.

Role of complement in myasthenia gravis.

San P, Jacob S Front Neurol. 2023; 14:1277596.

PMID: 37869140 PMC: 10585143. DOI: 10.3389/fneur.2023.1277596.

Individual myasthenia gravis autoantibody clones can efficiently mediate multiple mechanisms of pathology.

Pham M, Masi G, Patzina R, Obaid A, Oxendine S, Oh S Acta Neuropathol. 2023; 146(2):319-336.

PMID: 37344701 PMC: 11380498. DOI: 10.1007/s00401-023-02603-y.

References

Lindstrom J, Walter B, Einarson B . Immunochemical similarities between subunits of acetylcholine receptors from Torpedo, Electrophorus, and mammalian muscle. Biochemistry. 1979; 18(21):4470-80. DOI: 10.1021/bi00588a004. View

Lindstrom J . Autoimmune response to acetylcholine receptors in myasthenia gravis and its animal model. Adv Immunol. 1979; 27:1-50. DOI: 10.1016/s0065-2776(08)60261-8. View

Patrick J, Lindstrom J . Autoimmune response to acetylcholine receptor. Science. 1973; 180(4088):871-2. DOI: 10.1126/science.180.4088.871. View

Weill C, McNamee M, Karlin A . Affinity-labeling of purified acetylcholine receptor from Torpedo californica. Biochem Biophys Res Commun. 1974; 61(3):997-1003. DOI: 10.1016/0006-291x(74)90254-x. View

Lennon V, Lindstrom J, Seybold M . Experimental autoimmune myasthenia: A model of myasthenia gravis in rats and guinea pigs. J Exp Med. 1975; 141(6):1365-75. PMC: 2189842. DOI: 10.1084/jem.141.6.1365. View

Kohler G, Milstein C . Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975; 256(5517):495-7. DOI: 10.1038/256495a0. View

RAFTERY M, Vandlen R, Reed K, Lee T . Characterization of Torpedo californica acetylcholine receptor: its subunit composition and ligand-binding properties. Cold Spring Harb Symp Quant Biol. 1976; 40:193-202. DOI: 10.1101/sqb.1976.040.01.021. View

Karlin A, Weill C, McNamee M, Valderrama R . Facets of the structures of acetylcholine receptors from Electrophorus and Torpedo. Cold Spring Harb Symp Quant Biol. 1976; 40:203-10. DOI: 10.1101/sqb.1976.040.01.022. View

Changeux J, Benedetti L, Bourgeois J, Brisson A, Cartaud J, Devaux P . Some structural properties of the cholinergic receptor protein in its membrane environmental relevant to its function as a pharmacological receptor. Cold Spring Harb Symp Quant Biol. 1976; 40:211-30. DOI: 10.1101/sqb.1976.040.01.023. View

10.

Lindstrom J, Einarson B, Lennon V, Seybold M . Pathological mechanisms in experimental autoimmune myasthenia gravis. I. Immunogenicity of syngeneic muscle acetylcholine receptor and quantitative extraction of receptor and antibody-receptor complexes from muscles of rats with experimental.... J Exp Med. 1976; 144(3):726-38. PMC: 2190402. DOI: 10.1084/jem.144.3.726. View

11.

Lindstrom J, Engel A, Seybold M, Lennon V, LAMBERT E . Pathological mechanisms in experimental autoimmune myasthenia gravis. II. Passive transfer of experimental autoimmune myasthenia gravis in rats with anti-acetylcholine recepotr antibodies. J Exp Med. 1976; 144(3):739-53. PMC: 2190413. DOI: 10.1084/jem.144.3.739. View

12.

Lindstrom J, Lennon V, Seybold M, Whittingham S . Experimental autoimmune myasthenia gravis and myasthenia gravis: biochemical and immunochemical aspects. Ann N Y Acad Sci. 1976; 274:254-74. DOI: 10.1111/j.1749-6632.1976.tb47691.x. View

13.

Kohler G, Milstein C . Derivation of specific antibody-producing tissue culture and tumor lines by cell fusion. Eur J Immunol. 1976; 6(7):511-9. DOI: 10.1002/eji.1830060713. View

14.

Engel A, Lindstrom J, LAMBERT E, Lennon V . Ultrastructural localization of the acetylcholine receptor in myasthenia gravis and in its experimental autoimmune model. Neurology. 1977; 27(4):307-15. DOI: 10.1212/wnl.27.4.307. View

15.

Kao I, Drachman D . Myasthenic immunoglobulin accelerates acetylcholine receptor degradation. Science. 1977; 196(4289):527-9. DOI: 10.1126/science.850793. View

16.

Eldefrawi A, Eldefrawi M, Albuquerque E, Oliveira A, Mansour N, Adler M . Perhydrohistrionicotoxin: a potential ligand for the ion conductance modulator of the acetylcholine receptor. Proc Natl Acad Sci U S A. 1977; 74(5):2172-6. PMC: 431098. DOI: 10.1073/pnas.74.5.2172. View

17.

Heinemann S, Bevan S, Kullberg R, Lindstrom J, Rice J . Modulation of acetylcholine receptor by antibody against the receptor. Proc Natl Acad Sci U S A. 1977; 74(7):3090-4. PMC: 431419. DOI: 10.1073/pnas.74.7.3090. View

18.

Claudio T, RAFTERY M . Immunological comparison of acetylcholine receptors and their subunits from species of electric ray. Arch Biochem Biophys. 1977; 181(2):484-9. DOI: 10.1016/0003-9861(77)90254-5. View

19.

Karlin A, Holtzman E, Valderrama R, Damle V, Hsu K, Reyes F . Binding of antibodies to acetylcholine receptors in Electrophorus and Torpedo electroplax membranes. J Cell Biol. 1978; 76(3):577-92. PMC: 2110000. DOI: 10.1083/jcb.76.3.577. View

20.

Froehner S, Karlin A, Hall Z . Affinity alkylation labels two subunits of the reduced acetylcholine receptor from mammalian muscle. Proc Natl Acad Sci U S A. 1977; 74(10):4685-8. PMC: 432012. DOI: 10.1073/pnas.74.10.4685. View