KIR: Diverse, Rapidly Evolving Receptors of Innate and Adaptive Immunity

Abstract

KIR genes have evolved in primates to generate a diverse family of receptors with unique structures that enable them to recognize MHC-class I molecules with locus and allele-specificity. Their combinatorial expression creates a repertoire of NK cells that surveys the expression of almost every MHC molecule independently, thus antagonizing the spread of pathogens and tumors that subvert innate and adaptive defense by selectively downregulating certain MHC class I molecules. The genes encoding KIR that recognize classical MHC molecules have diversified rapidly in human and primates; this contrasts with conservation of immunoglobulin- and lectin-like receptors for nonclassical MHC molecules. As a result of the variable KIR-gene content in the genome and the polymorphism of the HLA system, dissimilar numbers and qualities of KIR:HLA pairs function in different humans. This diversity likely contributes variability to the function of NK cells and T-lymphocytes by modulating innate and adaptive immune responses to specific challenges.

Reconstructing immune phylogeny: new perspectives

“…NK cells are primary innate immune sentinels for the detection of certain viral infections and malignant transformation. The main classes of NK-cell receptors in mammals are either related to C-type lectins or members of the IgSF, and they are expressed by NK cells and natural killer T (NKT) cells 61 . In humans, the main diversified NK-cell receptors are killer-cell immunoglobulin-like receptors (KIRs), which are activating or inhibitory TYPE I TRANSMEMBRANE PROTEINS with immunoglobulin C2 (constant) ectodomains.…”

“…The extracellular regions of Ly49 gene products are single C-type-lectin domains. Haplotypic variant and invariant genetic regions of KIRs and Ly49 proteins are interspersed similarly 62 ; extensive haplotypic variability in KIRs arises through meiotic recombination 61 . Certain KIRs and Ly49 proteins recognize MHC class I molecules.…”

“…The evolution of NITRs is extraordinarily rapid, even within a species, a characteristic that is shared by immunoglobulins, TCRs and KIRs, and this has been attributed to a gene BIRTH-AND-DEATH process 79 . The allelic and haplotypic variation in the NITR genes in a single strain of zebrafish is reminiscent of the variation in KIRs from various human subpopulations 61,62 . KIRs and NITRs share other features, including differential expression by individual cells and expression by NK cells and T cells 80 .…”

Associations of killer cell immunoglobulin-like receptor genes with complications of rheumatoid arthritis

“…In contrast, the latter, called killer cell immunoglobulin-like receptors (KIRs), are highly polymorphic and recognize relatively polymorphic HLA epitopes. [7][8][9] KIRs, originally discovered on NK cells, are also present on subpopulations of T lymphocytes. 10,11 KIR molecules exist as two or three immunoglobulin-likedomain inhibitory receptors with a long cytoplasmic tail (KIR2DL or KIR3DL) and activating receptors with a short cytoplasmic tail (KIR2DS or KIR3DS).…”

“…10,11 KIR molecules exist as two or three immunoglobulin-likedomain inhibitory receptors with a long cytoplasmic tail (KIR2DL or KIR3DL) and activating receptors with a short cytoplasmic tail (KIR2DS or KIR3DS). 7,8 A peculiarity of the KIR genetic system is its haplotypic polymorphism, that is, individuals differ both in number and in kind (inhibitory vs activating) of KIR genes in their genotype. Generally, KIR haplotypes are divided into two groups.…”