Myasthenogenic significance of synthetic α-subunit peptide 183–200 of Torpedo californica and human acetylcholine receptor

Effect of myasthenic IgG on degradation of junctional acetylcholine receptor

“…Our anti-AChR antibody is polyclonal and includes many antibodies raised against various AChR regions. Despite recent advances in research done with synthetic peptides of AChR (particularly the a-subunit) on T-cell epitopes and agretopes and on B-cell epitopes, the main immunogenic region has yet to be determined.2220359 Although various T-and B-cell epitopes have been proposed, they are not thought to be constant, even in the same 1238,48, 49 Mossman et al and Jermy et al offered two possible explanations for why the loss of endplate AChR is not significantly correlated with the amount of antibody binding to AChR: (1) some MG patients may have antibodies that affect neuromuscular transmission by a mechanism that does not involve AChR34; and (2) some antibodies may bind to AChR in vivo without AChR loss, or with considerable delay before Sano et al have proposed that some antibodies present in extracellular fluids (with which serum IgG is equilibrated) lack access to their epitopes in vivo, but gain access to AChR when the muscle's plasma membrane is fragmented during h o m o g e n i z a t i~n .~~ Why, in our results, were the mean DR and MG scores significantly correlated? We believe that our in vivo study reflects only those pathogenic antibodies that have the ability to accelerate AChR degradation by crosslinking or by complement activation, thereby producing the good correlation between the mean DR and MG scores.…”

Removal of Pathogenic Autoantibodies by Immunoadsorption

“…Immunization of Lewis rats with the Torpedo californica and human segments of α183‐200 induces myasthenic features, as evidenced by elevated antipeptide antibodies and reduced endplate potential amplitudes 27. In contrast, α67‐76 fails to induce disease, unless artificially linked to a putative T cell stimulatory site, α106‐116.…”

Immunoadsorption in Myasthenia Gravis Based on Specific Ligands Mimicking the Immunogenic Sites of the Acetylcholine Receptor

“…The Torpedo californica and human sequences of AChR alpha 183‐200 were selected as immunogens for the animal experiment. The repeated immunization with the corresponding peptides, emulsified with complete Freund's adjuvant, caused Lewis rats to be myasthenic as evidenced by highly elevated antipeptide antibodies which reacted with the rat native AChR in the manner of blocking (expressed as the percentage inhibition of 125 I‐labeled alpha‐bungarotoxin‐binding to rat‐AChR by the immunized rat serum) (Table 1) and by reduced miniature endplate potential amplitudes (Table 1)(6).…”

“…The search for epitopes bearing on AChR which are implicated as targets for myasthenic antibodies has developed through the molecular information about the primary structure of AChR precursor (2) and the predicted transmembrane topography (3). Based on this, myasthenic domains in the AChR molecular structure, particularly in its alpha‐subunit, have been localized at the segments alpha 67‐76 (4) and alpha 125‐147 (5) as the sites recognized by antibodies implicated in the acceleration of AChR degradation and the destruction of postsynaptic membrane in cooperation with complements (termed binding antibodies, or modulating antibodies ) and at the segment alpha 183‐200 (6) as the site recognized by antibodies preventing the binding of ACh to AChR (termed blockng antibodies ) (Fig. 1).…”