[Molecular biology and immunology of acetylcholine receptor in relation to myasthenia gravis].
In search for the myasthenogenic sites in the molecular structure of acetylcholine receptor (AChR) alpha-subunit, the conformation-dependent B-cell epitopes, and the MHC class II-restricted, immune cofactors-modified T-cell epitopes were studied. Using the peptides synthesized corresponding to AChR amino acid sequence, the alpha 183-200 (as an antigen to raise "blocking antibody") and the alpha 70-90, alpha 125-147 and alpha 67-76 with alpha 107-116 (as antigens to raise "binding antibody") were found immunogenic in the induction of the disease in animals. Phenotypic changes in the T-cell lineages in the thymus were discussed. An impairment of excitation-contraction coupling in some of myasthenic muscles was attributed to a defect caused by antibodies raised against ryanodine receptor protein. Myasthenia gravis patients' sera containing anti-ryanodine receptor antibodies inhibited the calcium-induced release of calcium in response to caffeine in human rhabdomyosarcoma cell line. Buffalo/Mna rats with spontaneous benign thymoma showed (1) ryanodine receptor expressed in the thymic epithelial cells, (2) anti-ryanodine receptor antibodies in serum, and (3) reduced twitch and tetanic force without abnormality in synaptic transmission and muscle membrane properties. It is suggested that thymic epithelial cell and skeletal muscle share common ryanodine receptor antigen. The finding seen in this rat strain can be a counterpart of the feature reflecting an immune attack directed against a compartment of skeletal muscle in myasthenia gravis.
Takamori
M
M
Department of Neurology, Kanazawa University School of Medicine.
Komai
K
K
Iwasa
K
K
Yoshikawa
H
H
D000818:Animals; D001323:Autoantibodies; D015551:Autoimmunity; D006801:Humans; D008214:Lymphocytes / Q000276:immunology; D009157:Myasthenia Gravis / Q000276:immunology*; D051381:Rats; D011950:Receptors, Cholinergic / Q000276:immunology / Q000502:physiology; D019837:Ryanodine Receptor Calcium Release Channel / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology
D001323:Autoantibodies; D011950:Receptors, Cholinergic; D019837:Ryanodine Receptor Calcium Release Channel