KiR

Killer-cell immunoglobulin-like receptors (KIRs) are a family of receptors expressed mainly on natural killer (NK) cells and some T cells. They regulate responses to cells that lack or alter expression of major histocompatibility complex (MHC) class I molecules. KIRs are encoded by a gene cluster on human chromosome 19 and comprise multiple genes and alleles whose presence and sequence vary between individuals and populations. The extracellular domain structure classifies receptors as 2D or 3D, and cytoplasmic tails distinguish inhibitory receptors with long tails (KIR-L) bearing ITIM motifs from activating receptors with short tails that associate with adaptor proteins such as DAP12.

Ligand recognition tends to be focused on classical MHC class I molecules. Canonical interactions include KIR3DL1 binding to HLA-B Bw4 alleles, KIR2DL1 to HLA-C2, and KIR2DL2/3 to HLA-C1; activating counterparts such as KIR2DS1 and others can recognize some of the same ligands but typically with lower affinity or context-dependent signaling.

Functionally, KIRs modulate NK cell activity during development (education/licensing) and in responses to infection, malignancy, and transplantation. Engagement of inhibitory KIRs dampens cytotoxicity, while activating KIRs can promote NK cell killing when appropriate.

Genetic diversity is high in the KIR region, with substantial gene-content variability and allelic polymorphism leading to haplotypes described as A and B. This diversity influences immune responses and has been associated with disease susceptibility and outcomes in pregnancy and transplantation. KIR research extends to other primates, where repertoires differ but share the same general role in innate immunity.