Short <i>KIR</i> Haplotypes in Pygmy Chimpanzee (Bonobo) Resemble the Conserved Framework of Diverse Human <i>KIR</i> Haplotypes

Rajalingam, Raja; Hong, Min-Cheol; Adams, Erin J.; Shum, Benny P.; Guethlein, Lisbeth A.; Parham, Peter

doi:10.1084/jem.193.1.135

Cited by 87 publications

(105 citation statements)

References 54 publications

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“…However, none of the aforementioned receptors has signaling properties or distributions similar to those reported for KIR2DL4 [11,14,[22][23][24]. By contrast, KIR3DL3, whose ligand and functionality are unknown, shares with KIR2DL4 having a single ITIM and being well conserved in different individuals of several primate species [32][33][34][48][49][50]. Therefore, although the structures of these two receptors are otherwise divergent, this convergent feature makes it worth considering whether they might substitute for some of each other's functions.…”

Section: Discussionmentioning

confidence: 93%

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: Discussionmentioning

confidence: 93%

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, 2DL4 is highly conserved not only in pygmy chimpanzee (Bonobo) (44), but also in rhesus monkey (Macaca mulatta) (45), suggesting that 2DL4 serves an important role in primates. Important insights regarding the functions of 2DL4 have emerged from several recent findings.…”

Section: Discussionmentioning

confidence: 99%

SHP-1- and Phosphotyrosine-Independent Inhibitory Signaling by a Killer Cell Ig-Like Receptor Cytoplasmic Domain in Human NK Cells

Yusa

Catina

Campbell

2002

The Journal of Immunology

116

146

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Killer cell Ig-like receptors (KIR) are MHC class I-binding immunoreceptors that can suppress activation of human NK cells through recruitment of the Src homology 2-containing protein tyrosine phosphatase-1 (SHP-1) to two immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in their cytoplasmic domains. KIR2DL4 (2DL4; CD158d) is a structurally distinct member of the KIR family, which is expressed on most, if not all, human NK cells. 2DL4 contains only one ITIM in its cytoplasmic domain and an arginine in its transmembrane region, suggesting both inhibitory and activating functions. While 2DL4 can activate IFN-γ production, dependent upon the transmembrane arginine, the function of the single ITIM of 2DL4 remains unknown. In this study, tandem ITIMs of KIR3DL1 (3DL1) and the single ITIM of 2DL4 were directly compared in functional and biochemical assays. Using a retroviral transduction method, we show in human NK cell lines that 1) the single ITIM of 2DL4 efficiently inhibits natural cytotoxicity responses; 2) the phosphorylated single ITIM recruits SHP-2 protein tyrosine phosphatase, but not SHP-1 in NK cells; 3) expression of dominant-negative SHP-1 does not block the ability of 2DL4 to inhibit natural cytotoxicity; 4) surprisingly, mutation of the tyrosine within the single ITIM does not completely abolish inhibitory function; and 5) this correlates with weak SHP-2 binding to the mutant ITIM of 2DL4 in NK cells and a corresponding nonphosphorylated ITIM peptide in vitro. These results reveal new aspects of the KIR-inhibitory pathway in human NK cells, which are SHP-1 and phosphotyrosine independent.

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“…The similarities of the promoters and their regulation may ensure that the control of any novel KIR combination is readily facilitated. Significantly, the KIR2DL4 gene is well conserved in primates (61,63,64) and has qualitatively different regulation from the other KIR. The large differences demonstrated between the promoter of KIR2DL4 and those of variegated KIR may provide an explanation for the distinct phenotypes of these genes.…”

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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Short KIR Haplotypes in Pygmy Chimpanzee (Bonobo) Resemble the Conserved Framework of Diverse Human KIR Haplotypes

Cited by 87 publications

References 54 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

SHP-1- and Phosphotyrosine-Independent Inhibitory Signaling by a Killer Cell Ig-Like Receptor Cytoplasmic Domain in Human NK Cells

Different and Divergent Regulation of the KIR2DL4 and KIR3DL1 Promoters

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