Natural killer cell immunoglobulin-like receptor (KIR) locus profiles in African and South Asian populations

Norman, Paul J.; Carrington, Christine V. F.; Byng, M C; Maxwell, Lynn D; Curran, Martin D.; Stephens, Henry A.F.; Chandanayingyong, Dasnayanee; Verity, David H.; Hameed, Kamran; Ramdath, D. Dan; Vaughan, R. W.

doi:10.1038/sj.gene.6363836

Cited by 152 publications

(181 citation statements)

References 31 publications

(58 reference statements)

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“…Existence of similar haplotypes in two South Asian individuals has recently been proposed [38], but the evidence supporting the deletion of KIR2DL4 was so far based on the negative results obtained with a limited PCR-SSP assay and two oligonucleotide probes ( [38] and this study), which could also be explained by unrecognized polymorphisms of this gene. To rule out this possibility, we explored further the presence of KIR2DL4 in the genome of GB11 using seven additional PCR primer pairs, as detailed in Sect.…”

Section: An Unusual Kir Haplotype Lacking Centralmentioning

confidence: 83%

“…1). The absence of 3DP1 and both of 3DL1 and 3DS1 is remarkable because, like 2DL4, these are considered "framework" genes due to their ubiquitous presence in different KIR haplotypes [26,[30][31][32][33][34][35][36][37][38][39][40]. KIR2DL4, 3DP1 and 3DL1/3DS1 are contiguous genes in the central region of the KIR gene cluster, 2DL4 being in the middle of 3DP1 (centromeric) and 3DL1/ 3DS1 (telomeric) [33,34].…”

Section: An Unusual Kir Haplotype Lacking Centralmentioning

confidence: 99%

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Recognition of HLA‐G by the NK cell receptor KIR2DL4 is not essential for human reproduction

et al. 2003

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A central issue of reproductive immunology in mammals is why a semi-allogeneic embryo is not rejected by the pregnant mother. This is particularly intriguing since, in different species, the early pregnant uterus is infiltrated by numerous maternal lymphocytes, predominantly NK cells. The human NK cell receptor KIR2DL4 has been implicated in the maternal tolerance to the embryo due to its recognition of HLA-G, a non-classical MHC molecule expressed preferentially in the placenta. Killer cell Ig-like receptors (KIR) are believed to participate in the natural immunity to infection and tumors, but KIR2DL4 has unique structural, functional and genetic features that could confer it a different role. However, we demonstrate here that the KIR2DL4:HLA-G interaction is not essential for human reproduction by showing that a multiparous woman lacks a KIR2DL4 gene.

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Section: An Unusual Kir Haplotype Lacking Centralmentioning

confidence: 83%

Section: An Unusual Kir Haplotype Lacking Centralmentioning

confidence: 99%

Recognition of HLA‐G by the NK cell receptor KIR2DL4 is not essential for human reproduction

et al. 2003

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“…In addition, KIR2DL1, KIR2DL3, KIR2DS4 and KIR3DL1 genes within the A haplotype were present in over 84% of all individuals, a finding paralleled in other ethnic groups (Table 1; see Supplementary Table 1 for gf differences between Manitoban populations and details regarding the presence of KIR2DL5A and KIR2DL5B in these cohorts). [19][20][21][22] Conversely, marked variation was apparent in the genes associated with the B haplotype. Compared with Caucasian samples, the Aboriginal population exhibited a decreased presence of B haplotype centromeric genes KIR2DL2, KIR2DS2, as well as KIR2DS3 (Table 1).…”

Section: Resultsmentioning

confidence: 99%

The potential influence of KIR cluster profiles on disease patterns of Canadian Aboriginals and other indigenous peoples of the Americas

et al. 2011

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Genetic differences in immune regulators influence disease resistance and susceptibility patterns. There are major health discrepancies in immune-mediated diseases between Caucasians and Canadian Aboriginal people, as well as with other indigenous people of the Americas. Environmental factors offer a limited explanation as Aboriginal people also demonstrate a rare resistance to chronic hepatitis C virus infection. Killer immunoglobulin-like receptors (KIRs) are known modulators of viral responses and autoimmune diseases. The possibility that variation in KIR cluster profiles contribute to the health outcomes of Aboriginal people was evaluated with Canadian Caucasian (n¼93, population controls) and Aboriginal (n¼86) individuals. Relative to Caucasians, the Aboriginal KIR cluster displayed a greater immune activating phenotype associated with genes of the B haplotype situated within the telomeric region. In conjunction, there was a decrease in the genes of the B haplotype from the centromeric region. Caucasian and Aboriginal cohorts further demonstrated distinct genotype and haplotype relationships enforcing the disconnect between the B haplotype centromeric and telomeric regions within the Aboriginal population. Moreover, Caucasian KIR cluster patterns reflected studies of Caucasians globally, as well as Asians. In contrast, the unique pattern of the Canadian Aboriginal cohort mirrored the phenotype of other indigenous peoples of the Americas, but not that of Caucasians or Asians. Taken together, these data suggest that historically indigenous peoples of the Americas were subject to immune selection processes that could be influencing the current disease resistance and susceptibility patterns of their descendents.

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“…52 PCR-SSOP was carried out to confirm the presence or absence of KIR genes in Northern and Republic of Ireland populations as previously described. KIR gene and genotype frequencies of an additional 36 global population (4218 individuals from 38 different studies) were obtained from the published literature (35 populations [31][32][33]46,48,49,[53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68][69][70][71] ) and from an online database www.allelefrequencies.net. 72 Genotypes were classified as follows: the absence of 2DL2, 2DL5, 3DS1, 2DS1, 2DS2, 2DS3 or 2DS5 indicates that an individual is homozygous for the A genotype (that is, AA).…”

Section: Kir Typingmentioning

confidence: 99%

Receptor systems controlling natural killer cell function are genetically stratified in Europe

et al. 2009

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Natural killer (NK) cells are components of the innate immune system that function in identifying and destroying aberrant or pathogen-infected cells. These functions are largely controlled by killer cell immunoglobulin-like receptors (KIRs). KIRs inhibit and activate NK cell functions through interactions with their ligands, epitopes encoded by human leukocyte antigen (HLA) class I genes (HLA-C1, C2 and Bw4). Genes that encode KIR and their HLA ligands vary in frequency across human populations. Here, we characterize two Irish populations for KIR and HLA and determine the spatial distribution of functionally important KIR:HLA systems in Europe, a region known for its considerable underlying genetic stratification. We find that Southern Europe is a region characterized by higher frequencies of activatory KIR and strong inhibitory HLA ligand systems (2DL1:HLA-C2 and 3DL1:Bw4). A lower frequency of activatory KIR and the predominance of a comparatively weaker inhibitory ligand system (2DL3:HLA-C1) are observed northwards. Despite contrasting KIR:HLA systems in Northern and Southern Europe, there is a clear balance between inhibitory and activatory repertoires, and their ligands in both regions. These findings show 'functional stratification' of the epistatic KIR:HLA receptor system in Europe, the presence of which will likely affect NK cell-mediated immunity across different populations.

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Natural killer cell immunoglobulin-like receptor (KIR) locus profiles in African and South Asian populations

Abstract: Natural killer (NK) and some T cells express killer cell immunoglobulin-like receptors (KIRs),

Cited by 152 publications

References 31 publications

Recognition of HLA‐G by the NK cell receptor KIR2DL4 is not essential for human reproduction

Recognition of HLA‐G by the NK cell receptor KIR2DL4 is not essential for human reproduction

The potential influence of KIR cluster profiles on disease patterns of Canadian Aboriginals and other indigenous peoples of the Americas

Receptor systems controlling natural killer cell function are genetically stratified in Europe

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