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Myasthenogenicity of the main immunogenic region
Author(s) -
Lindstrom Jon,
Luo Jie
Publication year - 2012
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2012.06766.x
Subject(s) - acetylcholine receptor , myasthenia gravis , extracellular , autoantibody , nicotinic agonist , microbiology and biotechnology , chemistry , receptor , autoimmunity , stimulation , biology , immunology , biochemistry , endocrinology , antibody
In myasthenia gravis (MG) and experimental autoimmune MG (EAMG), many pathologically significant autoantibodies are directed to the main immunogenic region (MIR) of muscle nicotinic acetylcholine receptors (AChRs), a conformation‐dependent region at the extracellular tip of α1 subunits of AChRs. Human muscle AChR α1 MIR sequences were integrated into Aplesia ACh‐binding protein (AChBP). The chimera potently induced EAMG, while AChBP induced EAMG much less potently. AChBP is a water‐soluble protein resembling the extracellular domain of AChRs; yet, rats immunized with chimeras developed autoantibodies to both extracellular and cytoplasmic domains of muscle AChRs. We propose that an initial autoimmune response directed at the MIR leads to an autoimmune response sustained by muscle AChRs. Autoimmune stimulation sustained by endogenous muscle AChR may be a target for specific immunosuppression. These studies show that the α1 MIR is highly myasthenogenic, and that AChR‐like proteins distantly related to muscle AChR can induce EAMG and, potentially, MG.