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  • Title: The main immunogenic region of the acetylcholine receptor. Structure and role in myasthenia gravis.
    Author: Tzartos SJ, Barkas T, Cung MT, Kordossi A, Loutrari H, Marraud M, Papadouli I, Sakarellos C, Sophianos D, Tsikaris V.
    Journal: Autoimmunity; 1991; 8(4):259-70. PubMed ID: 1718457.
    Abstract:
    Auto-antibodies to the nicotine acetylcholine receptor (AChR) cause the disease myasthenia gravis (MG). Animals immunized with AChR or receiving anti-AChR antibodies acquire MG symptoms. The majority of the monoclonal antibodies (mAbs) raised in rats against intact AChR bind to a region on the extracellular side of the AChR's alpha-subunit, the main immunogenic region (MIR). The major loop of the overlapping epitopes for several anti-MIR mAbs has been localised between residues 67-76 of the alpha-subunit. Anti-MIR mAbs are very potent in accelerating AChR degradation (antigenic modulation) in muscle cell cultures and transferring experimental MG in animals. Fab fragments of single anti-MIR mAbs when bound to the AChR inhibit two-thirds of the MG patients' antibodies from binding and from inducing antigenic modulation of the AChR. This suggest that the majority of the human MG antibodies are also directed against the MIR. It has however to be verified by direct experiments.
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