THE MAIN IMMUNOGENIC REGION OF THE ACETYLCHOLINE-RECEPTOR - STRUCTURE AND ROLE IN MYASTHENIA-GRAVIS

被引：43
作者：
TZARTOS, SJ
BARKAS, T
CUNG, MT
KORDOSSI, A
LOUTRARI, H
MARRAUD, M
PAPADOULI, I
SAKARELLOS, C
SOPHIANOS, D
TSIKARIS, V
机构：
[1] Dept. of Biochemistry, Hellenic Pasteur Institute, Athens, 11521, 127, Vas, Sofias Ave.
[2] Dept. of Biochemistry and Genetics, Medical School
[3] Laboratoire de Chimie-Physique Macromoleculaire, CNRS-UA-494, ENS1C-INPL, 54001, Nancy
[4] Dept. of Chemistry, University of loannina, 45110, Ioannina
来源：
AUTOIMMUNITY | 1991年 / 8卷 / 04期
关键词：
ACETYLCHOLINE RECEPTOR; MYASTHENIA GRAVIS; MAIN IMMUNOGENIC REGION; MONOCLONAL ANTIBODIES; AUTOIMMUNE DISEASES; EPITOPES;
D O I：
10.3109/08916939109007633
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
Auto-antibodies to the nicotine acetylcholine receptor (AChR) cause the disease myasthenia gravis (MG). Animals immunized with AChR or receiving anti-AChR antibodies acquire MG symptoms. The majority of the monoclonal antibodies (mAbs) raised in rats against intact AChR bind to a region on the extracellular side of the AChR's a-subunit, the main immunogenic region (MIR). The major loop of the overlapping epitopes for several anti-MIR mAbs has been localised between residues 67-76 of the a-subunit. Anti-MIR mAbs are very potent in accelerating AChR degradation (antigenic modulation) in muscle cell cultures and transferring experimental MG in animals. Fab fragments of single anti-MIR mAbs when bound to the AChR inhibit two-thirds of the MG patients' antibodies from binding and from inducing antigenic modulation of the AChR. This suggests that the majority of the human MG antibodies are also directed against the MIR. It has however to be verified by direct experiments. © 1991 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.
引用
收藏
页码：259 / 270
页数：12
相关论文
共 108 条
  • [1] Changeux J.-P., Devillers-Thiery A., Chemouilli P., Acetylcholine receptor, an allosteric protein, Science, 225, pp. 1335-1345, (1984)
  • [2] McCarthy M.P., Earnest J.P., Young E.F., Choe S., Stroud R.M., The molecular neurobiology of the acetylcholine receptor, Ann Rev Neurosci, 9, pp. 383-413, (1986)
  • [3] Numa S., Structure and function of ionic channels, Membrane Proteins: Structure, Function, Assembly in series Chemica Scripta, 27B, pp. 5-19, (1987)
  • [4] Maelicke A., Structure and function of the nicotinic acetylcholine receptor, Handb of Exp Pharmacol, 86, pp. 267-313, (1988)
  • [5] Hucho F., Oberthur W., Lottspeich F., The ion channel of the nicotinic acetylcholine receptor is formed by the homologous helices M II of the receptor subunits, FEBS Lett, 205, pp. 137-142, (1986)
  • [6] Giraudat J., Dennis M., Heidmann T., Haumont P.-Y., Lederer F., Changeux J.-P., Structure of the high-affinity binding site for noncompetitive blockers of the acetylcholine receptor: [3-H] chlorpromazine labels homologous residues in the β and δ chains, Biochemistry, 26, pp. 2410-2418, (1987)
  • [7] Oosterhuis H.J.G.H., Myasthenia Gravis, Clin Neurol Neurosurg Monogr, 5, pp. 1-269, (1984)
  • [8] Ann NY Acad Sci, 505, pp. 1-914, (1987)
  • [9] Lindstrom J., Shelton D., Fugii Y., Myasthenia Gravis, Advances in Immunology, 42, pp. 233-284, (1988)
  • [10] Engel A.G., Myasthenia gravis and myasthenic syndromes, Ann Neurol, 16, pp. 519-533, (1984)
12345678910