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Critical Reviews™ in Immunology

Impact factor: 3.698

ISSN Print: 1040-8401
ISSN Online: 2162-6472

Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v22.i5-6.70
20 pages

Variation Within the Human Killer Cell Immunoglobulin-Like Receptor ( KIR) Gene Family

Makoto Yawata
Stanford University, School of Medicine, Department of Structural Biology, 299 Campus Drive West, Stanford, CA 94305-5126
Nobuyo Yawata
Stanford University, School of Medicine, Department of Structural Biology, 299 Campus Drive West, Stanford, CA 94305-5126
Laurent Abi-Rached
Stanford University, School of Medicine, Department of Structural Biology, 299 Campus Drive West, Stanford, CA 94305-5126
Peter Parham
Stanford University, School of Medicine, Department of Structural Biology, 299 Campus Drive West, Stanford, CA 94305-5126

ABSTRACT

The killer cell immunoglobulin-like receptors (KIR) form a family of highly homologous immune receptors that regulate the response of natural killer (NK) cells and some T cells. The genetics of the human KIR family is reviewed in this article. In human populations, diversity in KIR genotype arises from variations in gene content and allelic polymorphism. Comparisons of 81 human KIR sequences reveal past events of gene duplication and recombination, and indicate that individual KIR genes have diversified from the influence of natural selection. Comparison and compilation of population studies reveal extensive KIR genotype variability within human populations and among them. Genomic analysis shows the KIR genes to be close to each other and separated by homologous sequences that promote haplotype diversification through assymetric recombination. In contrast, homologous recombination appears favored at a unique sequence in the center of the KIR locus, and much haplotypic diversity can be explained by recombination between a limited number of gene-content motifs in the centromeric and telomeric halves of the locus. The importance of NK cells for early defenses against infection suggests that human KIR genotype diversity is the accumulated consequence of a history of numerous and successive selective episodes by different pathogens on human NK-cell responses.