An autosomal dominant locus, Nka, mapping to the Ly-49 region of a rat natural killer (NK) gene complex, controls NK cell lysis of allogeneic lymphocytes.

Dissen, Erik; Ryan, James C.; Seaman, William E.; Fossum, Sigbjørn

doi:10.1084/jem.183.5.2197

Cited by 110 publications

(108 citation statements)

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“…As stated in the Introduction section, we now consider NKR-P1B PVG (previously referred to as NKR-P1C) to be a divergent allele of the NKR-P1B receptor in the F344 strain. The original F344 Nkrp1b sequence [2,17] is probably incorrect, however, as it deviates from more recent cDNA clones obtained from the F344-derived RNK-16 line (this report and [23]). The latter are identical with the deduced sequence in the BN strain, which is closely related with F344 in the NKC [16].…”

Section: Discussionmentioning

confidence: 55%

“…We have recently shown that mAb 3.2.3 (or 10/78) fails to stain NK cells from selected strains, analogous to the situation for the NK1.1 marker in mice [16]. The inhibitory NKR-P1B receptor was originally identified in the F344 strain but is present in BN as well and is also stained by mAb 3.2.3 [2,17,18]. Our attempts to amplify Nkrp1b transcripts by RT-PCR from the highly alloreactive PVG rat strain have repeatedly been unsuccessful (our unpublished data).…”

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confidence: 90%

“…Rodent Introduction NK cells express several families of killer cell lectin-like receptors (KLR). These are type II transmembrane proteins encoded by the NK gene complex (NKC), which is located on chromosome 4 in the rat [1,2]. The NKR-P1 molecules (KLRB or CD161) were among the first KLR to be characterized, but their function long remained elusive [3][4][5].…”

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Two major groups of rat NKR‐P1 receptors can be distinguished based on chromosomal localization, phylogenetic analysis and Clr ligand binding

et al. 2009

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A major subset of non-alloreactive NK cells in PVG strain rats is generally low in Ly49 receptors, but expresses the rat NKR-P1B PVG receptor (previously termed NKR-P1C). The NKR-P1B 1 NK subset is inhibited by a non-polymorphic target cell ligand, which we have shown here to be a C-type lectin-related molecule (Clr). Clr11 ligates two divergent NKR-P1B alleles as judged by an NFAT-driven reporter assay, and inhibits NK-cell cytotoxicity of NKR-P1B 1 NK cells. Clr11 also interacts with the prototypic NKR-P1A receptor and exerts a stimulatory influence on NK lysis. NKR-P1A and B are encoded by adjacent genes in the proximal part of the NK gene complex and show close sequence homology in their extracellular region. They diverge from another pair, NKR-P1F and -G, which is encoded by a second, distal Nkrp1 gene cluster. NKR-P1F and -G bind an overlapping panel of Clr ligands, but not Clr11. Rat Clr molecules appear to be constitutively expressed by hematopoietic cells; expression in tumor cell lines is more variable. The data show the existence of two phylogenetic groups of NKR-P1 molecules, which demonstrate conservation of ligand-binding properties independent of signaling function.Key words: Cytotoxicity . NK cells . Receptor . Rodent Introduction NK cells express several families of killer cell lectin-like receptors (KLR). These are type II transmembrane proteins encoded by the NK gene complex (NKC), which is located on chromosome 4 in the rat [1,2]. The NKR-P1 molecules (KLRB or CD161) were among the first KLR to be characterized, but their function long remained elusive [3][4][5]. Although the NKR-P1 family has expanded to include both activating and inhibitory members in rodents, it consists of only one member in several other mammalian species, including in human [6]. The nature of their ligands has been controversial [7,8], but it has recently been shown that members of another KLR-related receptor family, the C-type lectin-related (Clr) molecules [9], also termed C-type lectin 2D (CLEC2D), can act as ligands for certain NKR-P1 molecules [10,11]. The Clr gene family also shows considerable expansion in rodents and the Clr genes are interspersed with the Nkrp1 genes in the proximal (centromeric) part of the NKC. A recent analysis concluded that there are 11 Clr/Clec2d genes in the rat BN strain genome, which were numbered consecutively from proximal to distal. One of these (Clr8) is most likely only a gene fragment, which could have been excluded, but we will nevertheless adhere to the Clr numbering suggested by Hao et al. [6].In the mouse, the inhibitory NKR-P1B and -D receptors both bind Clrb (also termed Ocil). Clrb is constitutively expressed by hematopoietic cells and inhibits cytolytic activity of NKR-P1B/ D-expressing NK cells [10,11]. The activating NKR-P1F receptor has been shown to bind another Clr molecule, Clrg, by the use of a reporter assay and soluble recombinant proteins [11] functional consequence of this interaction remains obscure. In human, the NKR-P1A receptor binds a Clr orthologue term...

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Two major groups of rat NKR‐P1 receptors can be distinguished based on chromosomal localization, phylogenetic analysis and Clr ligand binding

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“…7,8 A gene distantly related to the Ig-like receptor gene family has recently also been detected in mice, but its relevance for rodent NK cell function has not been firmly established. 9 C-type lectin NK receptors, which occur in both inhibitory and activating forms and are encoded within a syntenic region on human chromosome 12, 10-13 mouse chromosome 6 14,15 and rat chromosome 4, 16 called the NK gene complex, can be sub-grouped into different families. Among these are the CD94/NKG2, the Ly49 and the NKR-P1 families.…”

Section: Introductionmentioning

confidence: 99%

The centromeric part of the human NK gene complex: linkage of LOX-1 and LY49L with the CD94/NKG2 region

et al. 2000

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The natural killer (NK) gene complex is a genomic region containing lectin-type receptor genes. We have established a contig of PAC and BAC clones comprising about 1 Mb of the centromeric part of the NK gene complex. This region extends from the LOX-1 gene, which encodes a receptor for oxidized LDL and was found within 100 kb telomeric of the STS marker D12S77, contains the CD94 and NKG2 NK receptor genes and reaches beyond D12S852 on the proximal side. In this part we have mapped the human LY49L gene, a homologue of the rodent Ly49 genes, which encode important MHC class I receptors for the regulation of NK cell activity in rodents. The LY49L gene is localized 100 to 200 kb centromeric of the NKG2 gene cluster and 300 to 400 kb telomeric of the STS marker D12S841. Genomic sequencing of the complete gene including promoter and intron sequences confirmed that the structure is similar to the mouse Ly49 genes. Screening of several cDNA libraries did not detect any transcripts of putative additional human LY49 genes. In addition, in the course of these studies several EST sequences were localized in the region, one immediately upstream of the LY49L gene. Genes and Immunity (2000) 1, 280-287.

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“…102 Moreover, loci contributing to susceptibility to cutaneous leishmaniasis, 103 insulin-dependent diabetes mellitus 104 and ectromelia virus 105 in mice have been also localized to this chromosomal region. In rats, Nka, an autosomal dominant locus that controls NK cell lysis of allogeneic lymphocytes 106 and Oia2, a locus controlling susceptibility to oil-induced arthritis has been mapped to the rat NKC. 107 Not surprisingly, the KIR in human has been associated with loci controlling innate or autoimmune immunity such as tumor killing 108 and rheumatoid arthritis.…”

Section: Mouse Models Of CMV Infectionmentioning

confidence: 99%

Genetic control of innate immune responses against cytomegalovirus: MCMV meets its match

2002

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Cytomegalovirus (CMV) is a widespread pathogen that is All Ly49 receptors characterized to date interact with MHC class I molecules on potential target cells, resulting in the accumulation of signals to the NK to either 'kill' or 'ignore' the cell based upon the repertoire of MHC class I molecules expressed. The identification of Cmv1 as Ly49H, a stimulatory member of the Ly49 family, adds an interesting twist to the Ly49 story. Although the ligand of Ly49H is not yet known, there is already compelling evidence that the ligand is upregulated on virally infected cells, resulting in specific activation of Ly49H-expressing NK cells. This review provides an historical perspective of the MCMV infection model from its inception to the discovery of the gene responsible for the phenotype and provides a basis for further experiments aimed at understanding the role of NK cells, in general, and Ly49H, in particular, in mediating resistance to cytomegalovirus.

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An autosomal dominant locus, Nka, mapping to the Ly-49 region of a rat natural killer (NK) gene complex, controls NK cell lysis of allogeneic lymphocytes.

Cited by 110 publications

References 61 publications

Two major groups of rat NKR‐P1 receptors can be distinguished based on chromosomal localization, phylogenetic analysis and Clr ligand binding

Two major groups of rat NKR‐P1 receptors can be distinguished based on chromosomal localization, phylogenetic analysis and Clr ligand binding

The centromeric part of the human NK gene complex: linkage of LOX-1 and LY49L with the CD94/NKG2 region

Genetic control of innate immune responses against cytomegalovirus: MCMV meets its match

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