Natural killer (NK) cells are more than simple killers and have been implicated in control and clearance of malignant and virally infected cells, regulation of adaptive immune responses, rejection of bone marrow transplants, and autoimmunity and the maintenance of pregnancy. Human NK cells largely use a family of germ-line encoded killer cell immunoglobulin-like receptors (KIR) to respond to the perturbations from self-HLA class I molecules present on infected, malignant, or HLA-disparate fetal or allogenic transplants. Genes encoding KIR receptors and HLA class I ligands are located on different chromosomes, and both feature extraordinary diversity in the number and type of genes. The independent segregation of KIR and HLA gene families produce diversity in the number and type of KIR-HLA gene combinations inherited in individuals, which may determine their immunity and susceptibility to diseases. This chapter provides an overview of NK cells and their unprecedented phenotypic and functional diversity within and between individuals.
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