dc.contributor.advisor | Morrison, Ivan | en |
dc.contributor.author | Hilton, Hugo Godfrey Harness | en |
dc.date.accessioned | 2017-11-09T11:36:56Z | |
dc.date.available | 2017-11-09T11:36:56Z | |
dc.date.issued | 2016-07-02 | |
dc.identifier.uri | http://hdl.handle.net/1842/25474 | |
dc.description.abstract | In 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.iso | en | |
dc.publisher | The University of Edinburgh | en |
dc.relation.hasversion | Hilton, 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.hasversion | Hilton, 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.hasversion | Hilton, 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.hasversion | Hilton, 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.hasversion | Hilton, 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.subject | MHC | en |
dc.subject | KIR | en |
dc.subject | immunogenetics | en |
dc.title | Evolution and function of variable NK cell receptors and their HLA class I ligands | en |
dc.type | Thesis or Dissertation | en |
dc.type.qualificationlevel | Doctoral | en |
dc.type.qualificationname | PhD(P) Doctor of Philosophy by Research Publications | en |