The conformation of the main immunogenic region on the alpha-subunit of muscle acetylcholine receptor is affected by neighboring receptor subunits.
Myasthenia gravis (MG) is caused by autoantibodies to the acetylcholine receptor (AChR). Experiments with fetal (alpha(2)betagammadelta) and adult (alpha(2)betaepsilondelta) AChR and with recombinant subunit dimers showed that some monoclonal antibodies (mAbs) against the main immunogenic region (MIR), located on the alpha-subunit of the AChR, bind better to fetal AChR and to alphagamma subunit dimer than to adult AChR and alphaepsilon dimer and equally to both alphabeta and alphadelta. However, other anti-MIR mAbs prefer adult AChR and alphaepsilon dimer, bind well to alphabeta but weakly to alphadelta. These results suggest that the MIR conformation is affected by the neighboring gamma/epsilon- and delta-subunits and may contribute to understanding the antibody specificities in MG.
Fostieri
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E
Department of Biochemistry, Hellenic Pasteur Institute, 127 Vas, Sofias Avenue 115 21 Athen, Greece.
Beeson
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D
Tzartos
S J
SJ
D000375:Aging / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D002460:Cell Line; D019281:Dimerization; D000939:Epitopes / Q000276:immunology; D005333:Fetus / Q000276:immunology; D051379:Mice; D009157:Myasthenia Gravis / Q000276:immunology*; D011487:Protein Conformation; D011863:Radioimmunoassay; D011950:Receptors, Cholinergic / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000939:Epitopes; D011950:Receptors, Cholinergic