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Title: Immunochemistry of the acetylcholine receptor
Author: Bird, Martin Charles
ISNI:       0000 0001 3465 0165
Awarding Body: University of Bath
Current Institution: University of Bath
Date of Award: 1985
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1. Anti-Torpedo marmorata AChR antibody fragments (Fab and F(ab')2) have been prepared from sheep immunised with Torpedo AChR, and exhibiting experimental autoimmune myasthenia gravis. The antibody fragments were labelled with 125I with the retention of antigen binding capacity. Labelled and unlabelled antibody fragments were used to study the antigenicity of soluble and membrane-bound AChR, Anti-receptor antibodies were found to reduce (?-toxin binding to the AChR This was demonstrated to be caused by steric hindrance rather than by direct blockade of the toxin binding site, or by antigenic modulation of the receptor. Removal of carbohydrate residues from the AChR resulted in no decrease in antibody binding, implying that carbohydrate made no direct contribution to the antigenicity of the receptor. Denaturation of the AChR resulted in a decrease in anti-receptor antibody binding of between 60 and 84%. Thus antibodies were directed mainly at conformation-dependent sites on the receptor. Substantial differences between the antigenic sites of soluble and membrane-bound receptors were found. 2. The contribution of antibody-mediated muscle cell lysis in the pathogenesis of myasthenia gravis has been studied, using a novel in vitro cytotoxicity assay based on 3H-carnitine uptake and release by muscle cells in culture. Cytolytic activity toward both chick and human embryonic muscle cell cultures was demonstrated in over 30% of myasthenic sera, suggesting that myolysis may be a major mechanism for AChR loss in myasthenia gravis. Heat-inactivation of the sera abolished their lytic activity, and it was not fully restored by the addition of guinea pig complement. Myolysis may be caused by antibodies other than anti-AChR antibodies present in myasthenic sera.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Biochemistry