KIR Gene Family

Author: David Baorto, MD, PhD
Written: 2011-04-17

Clinical significance

KIR (Killer cell Immunoglobulin-like Receptor) molecules, a novel category of lymphocyte receptors, are predominantly found on the surface of natural killer (NK) cells. Through their interaction with HLA class I molecules, they modulate NK cell activity, central to the ability of those cells to distinguish between healthy cells and those either infected or transformed. The KIR family of molecules demonstrates extensive diversity at the gene level, stemming from multiple genes as well as multiple alleles. As a result of this polymorphism, KIR genotype is unlikely to be identical between individuals (in a sense similar to their molecular ligand, HLA Class I). The relationship between KIR genotype and disease is beginning to be elucidated, and is likely to interact with HLA. Needless to say it is a growing area, but there is evidence that which KIR genes are expressed in an individual may be related to susceptibility to infections (e.g., HCV, HIV), autoimmune diseases, and certain cancers. Importantly, the success of hematopoietic cell transplantation for some leukemias may be closely tied to KIR type or KIR compatibility, and be an additional predictor (with HLA).

Nomenclature of KIR genes and alleles

The KIR genes have been classified under the CD nomenclature as a set of CD158 molecules (CD158a, CD158b, etc.), but the CD names are not commonly used because they do not specifically reflect structure, function and gene polymorphism. The frequently used KIR gene nomenclature is developed by the HUGO Genome Nomenclature committee (HGNC). It includes over 15 genes and is based on molecular structure. They all begin with “KIR”, the next digit is the number of Immunoglobulin-like domains, next is “D” for domain, next is a description of the cytoplasmic tail, either “L” for long, “S” for short, or “P” for pseudogenes. The last digit is an integer to distinguish among different KIR genes having that same structure (e.g., KIR2DL1, KIR2DL2, etc.). Different alleles of a KIR gene are named in a fashion similar to that of HLA alleles, with an asterisk following the gene name, followed by digits indicating differences in encoded proteins and non-coding regions.

References

Marsh S G, Parham P, Dupont B, Geraghty D E, Trowsdale J, Middleton D, Vilches C, Carrington M, Witt C, Guethlein L A, Shilling H, Garcia C A, Hsu K C, Wain H. Killer-cell immunoglobulin-like receptor (KIR) nomenclature report, 2002. Immunogenetics 2003; 55(4):220-226. PubMed: 12838378.

Parham P. MHC class I molecules and KIRs in human history, health and survival. Nat Rev Immunol. 2005; 5(3):201-214. PubMed: 15719024.

Carrington M, Norman P. The KIR Gene Cluster. Bethesda (MD): National Center for Biotechnology Information (US); May 28, 2003. PubMed: NBK10135.

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