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dc.contributor.advisorMorrison, Ivanen
dc.contributor.authorHilton, Hugo Godfrey Harnessen
dc.date.accessioned2017-11-09T11:36:56Z
dc.date.available2017-11-09T11:36:56Z
dc.date.issued2016-07-02
dc.identifier.urihttp://hdl.handle.net/1842/25474
dc.description.abstractIn combating variable pathogens, mammalian immune systems have evolved diverse families of ligands and receptors. Epitomizing this strategy are the polymorphic major histocompatibility complex class I genes (termed HLA class I in humans) that encode ligands for highly variable natural killer (NK) cell receptors (in humans, the killer cell immunoglobulin-like receptors or KIR). Technological advances are poised to allow sequencing of these polymorphic genes, the most variable in the human genome, at the highest possible accuracy and resolution. However, studies that correlate immunogenetic polymorphisms with functional changes are in their infancy and often limited to those variants that combine high ligand avidity and high frequency in Caucasians. As a result, there is a paucity of information regarding the true scope of functional human immunogenetic diversity. This not only restricts our understanding of the evolution and function of the human immune system, but also underserves non-Caucasian populations with respect to disease association studies and therapeutic advances. The work presented in this thesis details original research and methodological advances that begin to address these functional shortfalls, the goal being to improve our understanding of the relationship between immunogenetic diversity, protein structure and immune function.en
dc.language.isoen
dc.publisherThe University of Edinburghen
dc.relation.hasversionHilton, H.G., et al., Mutation at positively selected positions in the binding site for HLA-C shows that KIR2DL1 is a more refined but less adaptable NK cell receptor than KIR2DL3. J Immunol, 2012. 189(3): p. 1418-30.en
dc.relation.hasversionHilton, H.G., et al., Loss and Gain of Natural Killer Cell Receptor Function in an African Hunter-Gatherer Population. PLoS Genet, 2015. 11(8): p. e1005439.en
dc.relation.hasversionHilton, H.G., et al., Polymorphic HLA-C Receptors Balance the Functional Characteristics of KIR Haplotypes. J Immunol, 2015. 195(7): p. 3160-70.en
dc.relation.hasversionHilton, H.G., et al., The production of KIR-Fc fusion proteins and their use in a multiplex HLA class I binding assay. J Immunol Methods, 2015. 425: p. 79-87.en
dc.relation.hasversionHilton, H.G. and P. Parham, Direct binding to antigen-coated beads refines the specificity and cross-reactivity of four monoclonal antibodies that recognize polymorphic epitopes of HLA class I molecules. Tissue Antigens, 2013. 81(4): p. 212-20.en
dc.subjectMHCen
dc.subjectKIRen
dc.subjectimmunogeneticsen
dc.titleEvolution and function of variable NK cell receptors and their HLA class I ligandsen
dc.typeThesis or Dissertationen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD(P) Doctor of Philosophy by Research Publicationsen


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