Evolution and function of variable NK cell receptors and their HLA class I ligands
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Date
02/07/2016Author
Hilton, Hugo Godfrey Harness
Metadata
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.