Immunogenetics of killer cell immunoglobulin-like receptors

The killer cell immunoglobulin receptor locus (KIR) on human chromosome 19 encodes activating and inhibitory receptors that are expressed principally by NK cells but also by subpopulations of T cells. For some of the KIR the ligands are known to be MHC class I molecules, for others ligands are elusive. In humans the KIR locus is highly diverse. KIR haplotypes differ in gene content and the individual genes exhibit allelic polymorphism; these two components work together to diversify haplotypes, which in pairwise combination diversify human KIR genotypes. The divergence of KIR between different human populations, as well as between closely related hominoid species, seem likely to be the products of balancing and directional selection upon the functions of KIR-expressing lymphocytes. Consistent with this model are the results of several studies associating KIR differences with disease susceptibility, immune responsiveness and events following allogeneic transplantation.