Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.605043
Title: A structural and kinetic analysis of antibody specificity
Author: James, L. C.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2000
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Abstract:
This thesis describes the characterisation of two unrelated antibodies, which have contrasting specificity and function. The first of these is a humanised IgF antibody called CAMPATH-1H, which has therapeutic properties due to its ability to target T and B lymphocytes. A complexed structure of the Fab in complex with a synthetic mimic of the native antigen was solved by x-ray crystallography to a resolution of 1.9Å. The structure has been used to dissect the detailed binding interactions between the antibody site and the antigen. This has revealed a number of unusual binding features, such as redundancy of the normally important contacting loop CDR H3. The interaction information has been used to suggest ways in which the functionality of the antibody could be improved, in terms of increasing the affinity and decreasing the immunogenicity when used in therapy. Comparisons of this bound structure to existing native structures of the original and humanised antibody has revealed differences that cannot be ascribed to the result of ligand binding. These differences suggest that here may be alternative pre-existing isomeric states of the antibody, one of which binds ligand preferentially. The poor resolution of one of the native structures and the potential influences of crystallisation on the structures, however, make these findings inconclusive. The above work lead to the characterisation of a second antibody, an IgE called SPE-7, with putative cross-reactive properties. The cloning of the SPE-7 Fab has permitted an analysis of the sequence in comparison to antibodies with known structure.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.605043  DOI: Not available
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