Cloning of Clr , a new family of lectin-like genes localized between mouse Nkrp1a and Cd69

Plougastel, Béatrice; Dubbelde, Chad; Yokoyama, Wayne M.

doi:10.1007/s002510100319

Cited by 77 publications

(86 citation statements)

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“…This implies, as suggested previously, that NKRP1D-Clr-b interactions may provide an alternative missing self-recognition system (11,12) in which disease-induced loss of protective Clr-b molecules from normal cells induces susceptibility to NK attack. Support for such a mechanism in the rat has been provided by the finding that rNKRP1C ϩ NK cells could kill syngeneic blasts in the presence of anti-NKRP1C mAb (37).…”

Section: Discussionmentioning

confidence: 62%

“…1), associate with SHP-1, and deliver inhibitory signals when cross-linked by mAbs or ligands (9 -12). A major breakthrough in our understanding of NKRP1 molecules was the discovery that the ligands of at least some NKRP1s belong to a family of related proteins, designated Clr proteins, encoded by genes interspersed among the Nkrp1 genes themselves (11)(12)(13). In particular, it was shown that NKRP1B/D recognizes Clr-b and that transfected cells expressing Clr-b are partially protected from lysis by NK cells, leading to the suggestion that NKRP1B/D-Clr-b recognition represents a novel form of missing-self-recognition designed to monitor cellular levels of Clr-b (11,12).…”

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confidence: 99%

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The Expression and Function of the NKRP1 Receptor Family in C57BL/6 Mice

Aust¹,

Gays²,

Mickiewicz³

et al. 2009

The Journal of Immunology

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NKRP1 receptors were discovered more than 20 years ago, but due to a lack of appropriate reagents, our understanding of them has remained limited. Using a novel panel of mAbs that specifically recognize mouse NKRP1A, D, and F molecules, we report here that NKRP1D expression is limited to a subpopulation of NK cells, but in contrast to Ly49 receptors appears to be expressed in a normal codominant manner. NKRP1D− and NKRP1D+ NK cells are functionally distinct, NKRP1D+ cells showing reduced expression of various Ly49 receptors, elevated expression of CD94/NKG2 receptors, and higher IFN-γ secretion and cytotoxicity than NKRP1D− cells. Furthermore, NKRP1D+ NK cells were unable to kill transfected cells expressing high levels of Clr-b molecules, but readily killed MHC class-I-deficient blast cells that express only low levels of Clr-b. NKRP1A and NKRP1F were expressed at low levels on all splenic and bone marrow NK cells, but mAb-induced cross-linking of NKRP1A and NKRP1F caused no significant enhancement or inhibition of NK cell cytotoxicity and no detectable production of IFN-γ. NKRP1A, D, and F expression could not be detected on NKT cells, all of which express NKRP1C, and although some activated T cells expressed NKRP1C and perhaps low levels of NKRP1A, no significant expression of NKRP1D or F could be detected. NKRP1 molecules expressed on NK cells or transfectants were down-regulated by cross-linking with mAbs or cell surface ligands, and using this phenomenon as a functional assay for NKRP1-ligand interaction revealed that NKRP1F can recognize CLR-x.

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Section: Discussionmentioning

confidence: 62%

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confidence: 99%

The Expression and Function of the NKRP1 Receptor Family in C57BL/6 Mice

Aust¹,

Gays²,

Mickiewicz³

et al. 2009

The Journal of Immunology

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“…In the C57/129 isoform, this is replaced by arginine, thereby precluding the formation of a conserved disulfide bond, found in all CRD crystal structures that have been solved, with the preceding conserved cysteine (C238 in Ly49B). The only other animal C-type lectins known to lack this conserved cysteine are the mouse Clr molecules (40) and their human ortholog LLT1 (41) that are encoded in the NKRP1 region of the NK complex and act as ligands for NKRP1 molecules (42)(43)(44)(45). In addition, several of the conserved core hydrophobic residues thought to be important for determining the basic structure of the CRD are altered in Ly49B.…”

Section: Discussionmentioning

confidence: 99%

Ly49B Is Expressed on Multiple Subpopulations of Myeloid Cells

Gays¹,

Aust²,

Reid

et al. 2006

The Journal of Immunology

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Using a novel mAb specific for mouse Ly49B, we report here that Ly49B, the last remaining member of the C57 Ly49 family to be characterized, is expressed at low levels on ∼1.5% of spleen cells, none which are NK cells or T cells but which instead belong to several distinct subpopulations of myeloid cells defined by expression of CD11b and different levels of Gr1. Much larger proportions of bone marrow and peritoneal cells expressed Ly49B, all being CD11b+ and comprising multiple subpopulations defined by light scatter, F4/80, and Gr1 expression. Costaining for Ly49Q, also expressed on myeloid cells, revealed that Ly49B and Ly49Q were most strongly expressed on nonoverlapping subpopulations, Ly49Qhigh cells being mostly B220+CD4+ and/or CD8+, Ly49B+ cells lacking these markers. Myeloid populations that developed from bone marrow progenitors in vitro frequently coexpressed both Ly49B and Ly49Q, and Ly49B expression could be up-regulated by LPS, α-IFN, and γ-IFN, often independently of Ly49Q. PCR analysis revealed that cultured NK cells and T cells contained Ly49B transcripts, and Ly49B expression could be detected on NK cells cultured in IL-12 plus IL-18, and on an immature NK cell line. Immunohistochemical studies showed that Ly49B expression in tissues overlapped with but was distinct from that of all other myeloid molecules examined, being particularly prominent in the lamina propria and dome of Peyer’s patches, implicating an important role of Ly49B in gut immunobiology. In transfected cells, Ly49B was found to associate with SHP-1, SHP-2, and SHIP in a manner strongly regulated by intracellular phosphorylation events.

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“…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.…”

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confidence: 99%

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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Cloning of Clr , a new family of lectin-like genes localized between mouse Nkrp1a and Cd69

Cited by 77 publications

References 0 publications

The Expression and Function of the NKRP1 Receptor Family in C57BL/6 Mice

The Expression and Function of the NKRP1 Receptor Family in C57BL/6 Mice

Ly49B Is Expressed on Multiple Subpopulations of Myeloid Cells

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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