Complexity and evolution of KIR genes in rhesus macaques

Abstract

Natural killer (NK) cells are essential in shaping immune responses against pathogens, and play an important role during pregnancy. Killer cell immunoglobulin-like receptors (KIR) educate the NK cell and determine its activation state. Because of this broad medical relevance, it is important to understand how this gene system has evolved. KIR genes have undergone rapid evolution in primates, as evidenced by extensive copy number variation and allelic diversity. Since KIR diversification appears to be primate species specific and might very well be pathogen driven, the aim of this thesis is to provide more insight into the KIR gene system of the rhesus macaque (Macaca mulatta). Therefore, this system has been thoroughly characterised on many levels, and one of the main conclusions to be drawn is that different types of selection have led to extensive levels of complexity. In this respect, the naturally occurring KIR in rhesus macaques may model the human situation, as a relatively small cohort of animals may comprise a KIR complexity equal to that observed in all human populations combined.