Multiple copies of KIR 3DL/S1 and KIR 2DL4 genes identified in a number of individuals

Williams, Fionnuala; Maxwell, Lynn D; Halfpenny, Iris; Meenagh, Ashley; Sleator, C.; Curran, Martin D.; Middleton, Derek

doi:10.1016/s0198-8859(03)00089-2

Cited by 44 publications

(61 citation statements)

References 15 publications

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“…KIR2DL4 duplications have, however, been implied in transcriptional analyses in rhesus macaques and humans, with up to three different KIR2DL4 sequences reported in a single subject (16,32,33). In line with these reports, 1 to 3 KIR2DL4 copies per cell were measured in the present study.…”

Section: Cd8␣supporting

confidence: 85%

KIR2DL4Copy Number Variation Is Associated with CD4⁺T-Cell Depletion and Function of Cytokine-Producing NK Cell Subsets in SIV-InfectedMamu-A*01-Negative Rhesus Macaques

Hellmann

Letvin

Schmitz

2013

J Virol

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Here, we demonstrate that KIR2DL4 copy number variation (CNV) is associated with CD4 + T-cell decline and functionality of cytokine-producing NK cells during primary simian immunodeficiency virus (SIV) infection in Mamu-A * 01 − Indian-origin rhesus macaques, with higher KIR2DL4 copy numbers being associated with a better preservation of CD4 + T cells and an increased gamma interferon (IFN-γ) production from stimulated cytokine-producing NK cell subsets during acute SIVmac251 infection. These findings underscore the crucial role of activating killer-cell immunoglobulin-like receptors (KIRs) in NK cell-mediated SIV responses during early SIV infection.

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Section: Cd8␣supporting

confidence: 85%

KIR2DL4Copy Number Variation Is Associated with CD4⁺T-Cell Depletion and Function of Cytokine-Producing NK Cell Subsets in SIV-InfectedMamu-A*01-Negative Rhesus Macaques

Hellmann

Letvin

Schmitz

2013

J Virol

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“…Within this study an unusual typing pattern, corresponding to a combination of three KIR2DL4 alleles (2DL4*00102, *00201, and *005), was identified in a number of cases [25]. DNA contamination was eliminated as a possible cause by performing HLA typing on the patients involved.…”

Section: Resultsmentioning

confidence: 84%

Investigation of killer cell immunoglobulinlike receptor gene diversity: I. KIR2DL4

Williams¹,

Meenagh²,

Sleator³

et al. 2004

Human Immunology

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“…However, most individuals carry only one or two of the three lineages. Family studies identified a KIR haplotype in Europeans that contains both 3DS1 and 3DL1 and likely was formed by unequal crossing over, which duplicated both the KIR2DL4 and 3DLl/S1 genes Williams et al 2003;Gomez-Lozano et al 2005). The potential benefit to such duplication haplotypes is that they permit some individuals to carry all three 3DL1/S1 allelic lineages.…”

Section: Kir3dl1/2v Generates Weaker Inhibition Than Kir3dl1mentioning

confidence: 99%

Meiotic recombination generates rich diversity in NK cell receptor genes, alleles, and haplotypes

Norman¹,

Abi-Rached²,

et al. 2009

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Natural killer (NK) cells contribute to the essential functions of innate immunity and reproduction. Various genes encode NK cell receptors that recognize the major histocompatibility complex (MHC) Class I molecules expressed by other cells. For primate NK cells, the killer-cell immunoglobulin-like receptors (KIR) are a variable and rapidly evolving family of MHC Class I receptors. Studied here is KIR3DL1/S1, which encodes receptors for highly polymorphic human HLA-A and -B and comprises three ancient allelic lineages that have been preserved by balancing selection throughout human evolution. While the 3DS1 lineage of activating receptors has been conserved, the two 3DL1 lineages of inhibitory receptors were diversified through inter-lineage recombination with each other and with 3DS1. Prominent targets for recombination were D0-domain polymorphisms, which modulate enhancer function, and dimorphism at position 283 in the D2 domain, which influences inhibitory function. In African populations, unequal crossing over between the 3DL1 and 3DL2 genes produced a deleted KIR haplotype in which the telomeric ''half'' was reduced to a single fusion gene with functional properties distinct from its 3DL1 and 3DL2 parents. Conversely, in Eurasian populations, duplication of the KIR3DL1/S1 locus by unequal crossing over has enabled individuals to carry and express alleles of all three KIR3DL1/S1 lineages. These results demonstrate how meiotic recombination combines with an ancient, preserved diversity to create new KIR phenotypes upon which natural selection acts. A consequence of such recombination is to blur the distinction between alleles and loci in the rapidly evolving human KIR gene family.

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Multiple copies of KIR 3DL/S1 and KIR 2DL4 genes identified in a number of individuals

Cited by 44 publications

References 15 publications

KIR2DL4Copy Number Variation Is Associated with CD4⁺T-Cell Depletion and Function of Cytokine-Producing NK Cell Subsets in SIV-InfectedMamu-A*01-Negative Rhesus Macaques

KIR2DL4Copy Number Variation Is Associated with CD4⁺T-Cell Depletion and Function of Cytokine-Producing NK Cell Subsets in SIV-InfectedMamu-A*01-Negative Rhesus Macaques

Investigation of killer cell immunoglobulinlike receptor gene diversity: I. KIR2DL4

Meiotic recombination generates rich diversity in NK cell receptor genes, alleles, and haplotypes

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Multiple copies of KIR 3DL/S1 and KIR 2DL4 genes identified in a number of individuals

Cited by 44 publications

References 15 publications

KIR2DL4Copy Number Variation Is Associated with CD4+T-Cell Depletion and Function of Cytokine-Producing NK Cell Subsets in SIV-InfectedMamu-A*01-Negative Rhesus Macaques

KIR2DL4Copy Number Variation Is Associated with CD4+T-Cell Depletion and Function of Cytokine-Producing NK Cell Subsets in SIV-InfectedMamu-A*01-Negative Rhesus Macaques

Investigation of killer cell immunoglobulinlike receptor gene diversity: I. KIR2DL4

Meiotic recombination generates rich diversity in NK cell receptor genes, alleles, and haplotypes

Contact Info

Product

Resources

About

KIR2DL4Copy Number Variation Is Associated with CD4⁺T-Cell Depletion and Function of Cytokine-Producing NK Cell Subsets in SIV-InfectedMamu-A*01-Negative Rhesus Macaques

KIR2DL4Copy Number Variation Is Associated with CD4⁺T-Cell Depletion and Function of Cytokine-Producing NK Cell Subsets in SIV-InfectedMamu-A*01-Negative Rhesus Macaques