Population Frequencies and Putative Haplotypes of the Killer Cell Immunoglobulin-Like Receptor Sequences and Evidence for Recombination1

Witt, Campbell S.; Dewing, Christopher B.; Sayer, D.; Uhrberg, Marcus; Parham, Peter; Christiansen, Frank

doi:10.1097/00007890-199912150-00024

Cited by 146 publications

(197 citation statements)

References 21 publications

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“…Frequencies of KIR types corresponded with published series. 14,20,24,25 Five KIR genes were almost universally expressed: 2DL4, 3DL2 and 3DL3 were present in 100% of the donors; all except one was positive for 2DL1 and all except two were positive for 2DL3 (Figure 1). The most frequent activating KIR genes were 2DS4*00101/00102/002 and 2DS4*003-005 found in 29 (58%) of the donors.…”

Section: Donor Kir Gene Frequenciesmentioning

confidence: 99%

Rapid natural killer cell recovery determines outcome after T-cell-depleted HLA-identical stem cell transplantation in patients with myeloid leukemias but not with acute lymphoblastic leukemia

et al. 2007

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Natural killer (NK) cells are the first lymphocytes to recover after allogeneic stem cell transplantation (SCT) and can exert powerful graft-versus-leukemia (GVL) effects determining transplant outcome. Conditions governing NK cell alloreactivity and the role of NK recovery in sibling SCT are not well defined. NK cells on day 30 post-transplant (NK30) were measured in 54 SCT recipients with leukemia and donor and recipient killer immunoglobulin-like receptor (KIR) genotype determined. In univariate analysis, donor KIR genes 2DL5A, 2DS1, 3DS1 (positive in 46%) and higher numbers of inhibitory donor KIR correlated with higher NK30 counts and were associated with improved transplant outcome. NK30 counts also correlated directly with the transplant CD34 cell dose and inversely with the CD3 þ cell dose. In multivariate analysis, the NK30 emerged as the single independent determinant of transplant outcome. Patients with NK30 4150/ll had less relapse (HR 18.3, P ¼ 0.039), acute graft-versus-host disease (HR 3.2, P ¼ 0.03), non-relapse mortality (HR 10.7, P ¼ 0.028) and improved survival (HR 11.4, P ¼ 0.03). Results suggest that T cell-depleted SCT might be improved and the GVL effect enhanced by selecting donors with favorable KIR genotype, and by optimizing CD34 and CD3 doses.

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Section: Donor Kir Gene Frequenciesmentioning

confidence: 99%

Rapid natural killer cell recovery determines outcome after T-cell-depleted HLA-identical stem cell transplantation in patients with myeloid leukemias but not with acute lymphoblastic leukemia

et al. 2007

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“…Up to 12 KIR genes appear to be expressed, and KIR haplotypes consist of various combinations of KIR genes (19,21). The number of putatively expressed KIR genes present on a single haplotype ranges from 7 to 11, depending primarily on the presence or absence of activating KIR loci (19,21,22). The most common Caucasian haplotype, the "A" haplotype (frequency of ϳ50%), contains only a single activating KIR gene, KIR2DS4, and six inhibitory KIR loci (21).…”

Section: ) Binding Of Inhibitory Kir (Designated 2dlmentioning

confidence: 99%

Cutting Edge: Susceptibility to Psoriatic Arthritis: Influence of Activating Killer Ig-Like Receptor Genes in the Absence of Specific HLA-C Alleles

Martin

Nelson

Lee

et al. 2002

The Journal of Immunology

305

223

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NK cell activity is partially controlled through interactions between killer Ig-like receptors (KIR) on NK cells and their respective HLA class I ligands. Independent segregation of HLA and KIR genes, along with KIR specificity for particular HLA allotypes, raises the possibility that any given individual may express KIR molecules for which no ligand is present. Inhibitory receptor genes KIR2DL2/3 and KIR2DL1 were present in nearly all subjects sampled in this study, whereas their respective activating homologs, KIR2DS2 and KIR2DS1, are each present in about half of the subjects. In this work we report that subjects with activating KIR2DS1 and/or KIR2DS2 genes are susceptible to developing psoriatic arthritis, but only when HLA ligands for their homologous inhibitory receptors, KIR2DL1 and KIR2DL2/3, are missing. Absence of ligands for inhibitory KIRs could potentially lower the threshold for NK (and/or T) cell activation mediated through activating receptors, thereby contributing to pathogenesis of psoriatic arthritis.

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“…The findings resonate with genomic features of the region. The KIR cluster on chromosome 19q13.4 appears to be evolving rapidly, and the numbers of loci within it vary extensively between haplotypes (25,61,62). The similarities of the promoters and their regulation may ensure that the control of any novel KIR combination is readily facilitated.…”

Section: Figure 3 (Continues)mentioning

confidence: 99%

Different and Divergent Regulation of the KIR2DL4 and KIR3DL1 Promoters

Stewart

Bergen

Trowsdale

2003

The Journal of Immunology

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The killer Ig-like receptors (KIR) are a family of highly related MHC class I receptors that show extreme genetic polymorphism both within the human population and between closely related primate species, suggestive of rapid evolutionary diversification. Most KIR are expressed in a variegated fashion by the NK population, giving rise to an NK repertoire of specificities for MHC class I. We compared the promoter for KIR3DL1, which exhibits variegated gene expression, with that for KIR2DL4, which is expressed by all NK cell clones. Maximum transcriptional activity of each was encoded within ∼270 bp upstream of the translation initiation codon. The KIR2DL4 promoter drove reporter gene expression only in NK cells, while the KIR3DL1 promoter was active in a range of cell types, suggesting that the latter requires other regulatory elements for physiological expression. In NK cells, reporter gene expression driven by the KIR2DL4 promoter was greater than that driven by the KIR3DL1 promoter. DNase I footprinting revealed that transcription factor binding sites differ between the two promoters. The data indicate that while the promoters of these two KIR genes share 67% nucleotide identity, they have evolved distinct properties consistent with different roles in regulating the generation of NK repertoire.

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Population Frequencies and Putative Haplotypes of the Killer Cell Immunoglobulin-Like Receptor Sequences and Evidence for Recombination1

Abstract: Typing for the presence of particular KIR genes may be indicated for bone marrow donor-recipient pairs for whom a class I HLA mismatch is unavoidable.

Cited by 146 publications

References 21 publications

Rapid natural killer cell recovery determines outcome after T-cell-depleted HLA-identical stem cell transplantation in patients with myeloid leukemias but not with acute lymphoblastic leukemia

Rapid natural killer cell recovery determines outcome after T-cell-depleted HLA-identical stem cell transplantation in patients with myeloid leukemias but not with acute lymphoblastic leukemia

Cutting Edge: Susceptibility to Psoriatic Arthritis: Influence of Activating Killer Ig-Like Receptor Genes in the Absence of Specific HLA-C Alleles

Different and Divergent Regulation of the KIR2DL4 and KIR3DL1 Promoters

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