The conformation of the main immunogenic region on the α-subunit of muscle acetylcholine receptor is affected by neighboring receptor subunits

Abstract

Myasthenia gravis (MG) is caused by autoantibodies to the acetylcholine receptor (AChR). Experiments with fetal (α 2βγδ) and adult (α 2βϵδ) AChR and with recombinant subunit dimers showed that some monoclonal antibodies (mAbs) against the main immunogenic region (MIR), located on the α-subunit of the AChR, bind better to fetal AChR and to αγ subunit dimer than to adult AChR and αϵ dimer and equally to both αβ and αδ. However, other anti-MIR mAbs prefer adult AChR and αϵ dimer, bind well to αβ but weakly to αδ. These results suggest that the MIR conformation is affected by the neighboring γ/ϵ- and δ-subunits and may contribute to understanding the antibody specificities in MG.