Antigenic structure of the human muscle nicotinic acetylcholine receptor main immunogenic region.
The main immunogenic region on the alpha1 subunits of muscle nicotinic acetylcholine receptors provokes half or more of the autoantibodies in myasthenia gravis and its animal model. Many of these autoantibodies depend on the native conformation of the receptor for their ability to bind with high affinity. We mapped this region and explained the conformation dependence of its epitopes by making chimeras in which sequences of human muscle alpha1 subunits were replaced in human neuronal alpha7 subunits or Aplysia acetylcholine binding protein. These chimeras also revealed that the main immunogenic region can play a major role in promoting conformational maturation and, consequently, assembly of receptor subunits.
Luo
Jie
J
Department of Neuroscience, Medical School of the University of Pennsylvania, Philadelphia, PA 19104-6074, USA. luoj3@mail.med.upenn.edu
Lindstrom
Jon
J
D000818:Animals; D000936:Antigen-Antibody Complex / Q000502:physiology*; D000941:Antigens / Q000737:chemistry / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006801:Humans; D018482:Muscle, Skeletal / Q000276:immunology* / Q000294:innervation / Q000378:metabolism; D009157:Myasthenia Gravis / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D009469:Neuromuscular Junction / Q000276:immunology* / Q000378:metabolism; D009865:Oocytes; D011487:Protein Conformation; D017434:Protein Structure, Tertiary / Q000502:physiology; D021122:Protein Subunits / Q000276:immunology; D051381:Rats; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000276:immunology; D014982:Xenopus laevis; D064569:alpha7 Nicotinic Acetylcholine Receptor
D000936:Antigen-Antibody Complex; D000941:Antigens; D001323:Autoantibodies; C579167:Chrna7 protein, human; C579165:Chrna7 protein, rat; D000939:Epitopes; D021122:Protein Subunits; D011978:Receptors, Nicotinic; D011993:Recombinant Fusion Proteins; D064569:alpha7 Nicotinic Acetylcholine Receptor
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