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Title: Autoantibodies to soluble cellular antigens
Author: Bunn, Christopher Charles
Awarding Body: University of London
Current Institution: Imperial College London
Date of Award: 1987
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Autoantibodies against a variety of soluble cellular components have been identified in the sera of patients with connective tissue diseases. Some specificities are recognised as having important clinical correlations that make them useful for diagnosis and treatment. Moreover, information about the structure and function of their antigens could provide an insight into the aetiology and pathogenesis of a range of autoimmune diseases. The aims of this project were to investigate the distribution of these autoantibodies in various diseases and to carry out molecular analysis of the antigens involved. A counterimmunoelectrophoresis assay was developed for the detection of antibodies to saline extractable tissue antigens. In addition to previously characterised systems, a number of new specificities were recognised, and their clinical associations and frequencies recorded. Their antigens were analysed by protein-A facilitated immunoprecipitation of radiolabelled protein or RRA from HeLa cell extracts. Antigens were shown to be proteins, or more rarely, some low frequency antibodies were shown to react with naked RRA, however the majority were ribonucleoprotein complexes. Three of the ribonucleoprotein antigens were associated almost exclusively with myositis and were considered for further study because of their simple immunoprecipitates consisting of a single polypeptide and a small RRA consistent in size with a tRRA. Inhibition of aminoacylation reactions by the antibodies involved identified the protein moieties of these complexes as aminoacyl tRRA synthetases specific for histidine, threonine and alanine. Furthermore anti-alanyl tRRA synthetase was shown to co-exist with antibody against cognate tRRA. Direct sequence analysis was used to confirm this identity, and the antibody was observed to bind to a nucleotide sequence in the anticodon loop. The implications of these results on synthetase recognition of tRRA, and on the generation of autoimmunity are discussed.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available