Breakage of tolerance to hidden cytoplasmic epitopes of the acetylcholine receptor in experimental autoimmune myasthenia gravis.
The acetylcholine receptor (AChR) is the major autoantigen in the antibody-mediated disease myasthenia gravis (MG) and its animal model experimental autoimmune myasthenia gravis (EAMG). This study demonstrates that rats immunized with a recombinant fragment corresponding to the normally exposed extracellular region of the rat AChR alpha-subunit first develop antibodies to the injected extracellular portion only, but later develop antibodies to intracellular cytoplasmic epitopes of AChR. The presence of autoantibodies to intracellular epitopes seems to be correlated with development of clinical signs of disease. We propose that a similar process of epitope spreading may take place in the natural course of myasthenia.
Feferman
Tali
T
Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
Im
Sin-Hyeog
SH
Fuchs
Sara
S
Souroujon
Miriam C
MC
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D001324:Autoantigens / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D003593:Cytoplasm / Q000235:genetics / Q000276:immunology*; D005110:Extracellular Space / Q000235:genetics / Q000276:immunology; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics; D016056:Immunodominant Epitopes / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D007279:Injections, Subcutaneous; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D021122:Protein Subunits / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D011950:Receptors, Cholinergic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D014101:Torpedo
D001323:Autoantibodies; D001324:Autoantigens; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D021122:Protein Subunits; D011950:Receptors, Cholinergic; D011993:Recombinant Fusion Proteins