KIR genes encode inhibitory receptors that reside on the surface of natural killer (NK) cell. NK cells are an important part of the innate immune system, responsible for defense against infected or cancer cells. The interaction of KIR receptors with HLA class I molecules regulates NK cell function by distinguishing between normal cells and infected or cancer cells.
The KIR locus is located on chromosome 19q13.4 within the leukocyte receptor complex (LRC) and is highly variable with regard to both gene content and allelic polymorphism. KIR genes are organized into the major haplotype groups A and B based on gene content (see figure below). Haplotype A is constant in gene content, consisting of 5 inhibitory genes and 1 activating gene, while haplotype B contains a variable number of inhibitory and activating genes.
A total of 15 human KIR genes and 2 pseudogenes have been identified, separated into centromeric and telomeric regions by the framework genes KIR3DP1 and KIR2DL4. Centromeric motifs can recombine freely with telomeric motifs, leading to a diverse number of haplotypes.
Recently, we identified 7 major gene content haplotypes, each representing different combinations of 4 centromeric and 2 telomeric gene motifs. After examining a further 9,024 chromosomes, we identified 37 rare gene-content haplotypes that varied from the 7 major haplotypes by gene deletions, insertions, and hybridizations (shown in figure above).