- Unraveling the genetic expression of the highly variable immune receptors of a killer
T.K. van den Berg
- Award date
- 23 September 2015
- Number of pages
- Document type
- PhD thesis
- Faculty of Medicine (AMC-UvA)
The Killer Immunoglobulin-like Receptors (KIRs) are a family of highly variable receptors which regulate cytotoxicity of Natural Killer (NK) cells and a subset of T-cells. The KIR genes, clustered on the genome in the KIR locus, are distributed unequally across the population due to variation in gene presence and gene copy number. However, although many different gene combinations have been found in the human Caucasian population, the studies described in this thesis show that there is a limited amount of patterns that define the KIR locus. The level of genetic variation seems to be caused mainly by the high rate of recombination events that occur at certain hot-spots in the locus.
A second layer of variation is found in the surface expression of the receptors on NK cells. Clonal expansion of individual cells, inter-allelic variation and variegated KIR expression levels all contribute to the complexity of KIR expression in humans. In addition, Interleukin-15 seems to be a potent regulator of KIR expression on NK cells, as was studied for both adult and neonatal cells.
All these factors make the KIR family potential players in several NK cell related disease settings. In this thesis, exploratory studies have been performed to study their association with the auto-immune disease Spondylo Arthropathy (AS). The data suggest that there may be a role for KIRs in progression of this disease.
In conclusion, the work in this thesis is centered on mapping KIR gene expression variation, to better understand its role in human disease.
- Research conducted at: Sanquin Research and Landsteiner Laboratory, Amsterdam, Department of Blood Cell Research
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