Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.415091
Title: Class I HLA supertype and supermotif definition by chemometric approaches
Author: Guan, Pingping
ISNI:       0000 0001 3521 6483
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 2005
Availability of Full Text:
Access through EThOS:
Full text unavailable from EThOS. Please try the link below.
Access through Institution:
Abstract:
Activation of cytotoxic T cells in human requires specific binding of antigenic peptides to human leukocyte antigen (HLA) molecules. HLA is the most polymorphic protein in the human body, currently 1814 different alleles collected in the HLA sequence database at the European Bioinformatics Institute. Most of the HLA molecules recognise different peptides. Also, some peptides can be recognised by several of HLA molecules. In the present project, all available class I HLA alleles are classified into supertypes. Super - binding motifs for peptides binding to some supertypes are defined where binding data are available. A variety of chemometric techniques are used in the project, including 2D and 3D QSAR techniques and different variable selection methods like SIMCA, GOLPE and genetic algorithm. Principal component analysis combined with molecular interaction fields calculation by the program GRID is used in the class I HLA classification. This thesis defines an HLA-A3 supermotif using two QSAR methods: the 3D-QSAR method CoMSIA, and a recently developed 2D-QSAR method, which is named the additive method. Four alleles with high phenotype frequency were included in the study: HLA-A*0301, HLA-A*1101, HLA-A*3101 and HLA- A*6801. An A*020T binding motif is also defined using amino acid descriptors and variable selection methods. Novel peptides have been designed according to the motifs and the binding affinity is tested experimentally. The results of the additive method are used in the online server, MHCPred, to predict binding affinity of unknown peptides. In HLA classification, the HLA-A, B and C molecules are classified into supertypes separately. A total of eight supertypes are observed for class I HLA, including A2, A3, A24, B7, B27, B44, CI and C4 supertype. Using the HLA classification, any newly discovered class I HLA molecule can be grouped into a supertype easily, thus simplifying the experimental function characterisation process.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.415091  DOI: Not available
Share: