Phylogenetic and functional conservation of the NKR-P1F and NKR-P1G receptors in rat and mouse

Kveberg, Lise; Dai, Ke-Zheng; Inngjerdingen, Marit; Brooks, Colin G.; Fossum, Sigbjørn; Vaage, John T.

doi:10.1007/s00251-011-0520-1

Cited by 28 publications

(57 citation statements)

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“…While NKR-P1B is expressed primarily by Ly49s3 − spleen NK cells, NKR-P1G is mainly expressed by Ly49s3 + cells (Fig. 1C, upper right and left plots, respectively), as predicted by previous mRNA studies [19]. The anti-NKR-P1F mAb ADA4 stained most spleen NK cells, NKT cells, and approximately 10% of conventional T cells (Fig.…”

Section: Resultsmentioning

confidence: 51%

“…3A). These results were somewhat surprising in the light of previous reporter assays, which had predicted Clr7, and not Clr4, as a strong ligand for NKR-P1G [19]. The identity of the Clr transfectants was confirmed by PCR (data not shown).…”

Section: Nkr-p1g Inhibits Cytotoxicity and Calcium Responses In Il-2-mentioning

confidence: 68%

“…Some alleles are so divergent they have mistakenly been characterized as novel proteins (rat NKR-P1B PVG as NKR-P1C [15], and mouse NKR-P1B B6 as NKR-P1D [30]. By contrast, NKR-P1F and NKR-P1G are strikingly conserved not only between different rat strains, but also between mouse and rat, both in terms of sequence and ligand specificity [19]. The amino acid sequences of NKR-P1F-and G predict opposite function.…”

Section: Introductionmentioning

confidence: 98%

“…The only organ showing expression of mouse Clr-a is the intestine [18], but unfortunately this has not yet been tested for rat Clr10. Our previous reporter cell studies have shown the presence of ligand(s) for both rat and mouse NKR-P1F and NKR-P1G receptors on a rat colon carcinoma cell line, suggesting expression in the rat intestinal compartment [19]. Also, recent data show that the mouse Clrf protein is expressed by intestinal epithelial cells, while NKR-P1G is expressed by IELs, which suggest that this receptor/ligand interaction is important for immunosurveillance of the mouse intestinal epithelium [40].…”

mentioning

confidence: 99%

“…The distal cluster harbors the NKR-P1F and NKR-P1G receptors, which have until now remained largely uncharacterized due to lack of suitable reagents. With chimeric NKR-P1 receptors and an artificial reporter cell system, we previously showed that NKR-P1F and NKR-P1G are promiscuous for a broad panel of rat and mouse Clr ligands, while NKR-P1A and NKR-P1B are specific for Clr11 [17,19]. Data from RT-PCR studies and in situ hybridization studies have shown that some mouse Clr molecules are broadly expressed, while others show more tissue-restricted expression.…”

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confidence: 99%

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Functional characterization of a conserved pair of NKR‐P1 receptors expressed by NK cells and T lymphocytes in liver and gut

et al. 2014

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Natural killer cell receptor protein 1 (NKR-P1) molecules are C-type lectin-like receptors modulating cellular responses toward target cells expressing C-type lectin-like related (Clr) molecules. Although the function of the prototypic rat NKR-P1A receptor and its inhibitory counterpart NKR-P1B are known, little is known about NKR-P1F and NKR-P1G apart from their promiscuity for Clr ligands. Here we generated mAbs against both receptors for phenotypic and functional analyses in rat tissues. NKR-P1F induced redirected lysis and robust Ca 2+ signaling in NK cells, which were prevented by simultaneous engagement of NKR-P1G. NKR-P1G also inhibited NK-cell lysis of Clr transfectants. NKR-P1F was expressed by most NK cells and NKR-P1A + T cells in all tissues analyzed, and by many NKR-P1A − intestinal T cells, while NKR-P1G was expressed by subsets of these cells with highest prevalence in gut and liver. In the intraepithelial compartment, the proportion of NKR-P1A + and NKR-P1F + cells was high at birth and thereafter declined, while NKR-P1B + and NKR-P1G + cells increased with age. Expression levels were also modulated by cytokines, with an increase of NKR-P1B and NKR-P1G induced by inflammatory cytokines, and a reduction of NKR-P1A by TGF-β. The physiological impact of NKR-P1 receptors might thus be dependent on age, tissue, and inflammatory status.Keywords: C-type lectin-related molecules r NK-cell receptors r NKR-P1 r Rodent Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionNatural killer (NK) cells are innate lymphoid cells with the ability to eliminate virally infected cells and transformed or allogeneic cells. They produce cytokines early in the immune response, and play an important role in shaping the immune response, e.g. in the context of inflammation and transplantation. These tasks are controlled by a wide range of receptors with different functions and ligands, such as Ly49 receptors, which recognize both classical and nonclassical MHC class I molecules, as well as MHC Correspondence: Dr. Lise Kveberg e-mail: lise.kveberg@rr-research.no class I-like virally encoded ligands [1][2][3]. Another family of MHCbinding receptors is the conserved NKG2/CD94 heterodimers, which bind the nonclassical MHC molecule HLA-E in human [4], its rodent homologue Qa-1 b in the mouse [5,6] and RT.BM1 in the rat [7]. Both the Ly49 and NKG2/CD94 receptor families contain inhibitory and activating members. NKG2D is a promiscuous activating receptor, recognizing several MHC class I-related ligands frequently upregulated upon cellular stress and associated with viral infection and malignant transformation [8].The activating NK cytotoxicity receptors react with several virus-derived and endogenous ligands [9,10].One of the earliest NK-cell receptors to be characterized was the NK-cell receptor protein 1A (NKR-P1A) in the rat, which is C 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu 502Lise Kveberg et al. Eur. J. Immunol. 2015. 45: 501-...

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Section: Resultsmentioning

confidence: 51%

Section: Nkr-p1g Inhibits Cytotoxicity and Calcium Responses In Il-2-mentioning

confidence: 68%

Section: Introductionmentioning

confidence: 98%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Functional characterization of a conserved pair of NKR‐P1 receptors expressed by NK cells and T lymphocytes in liver and gut

et al. 2014

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Analysis of the mouse 129-strain Nkrp1-Clr gene cluster reveals conservation of genomic organization and functional receptor–ligand interactions despite significant allelic polymorphism

et al. 2011

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The Nkrp1 (Klrb) family of NK cell receptors and their genetically linked Clr (Clec2) ligands are conserved between rodents and humans. Nonetheless, certain mouse and rat Nkrp1 genes exhibit significant allelic polymorphism between inbred strains. We previously demonstrated that the Nkrp1-Clr recognition system is genetically and functionally conserved between the B6 and BALB/c strains, with focused sequence divergence evident in certain genes (e.g., Nkrp1b,c). Here, we extend this finding by mapping the 129-strain Nkrp1-Clr gene cluster, which is structurally conserved yet displays significant sequence divergence relative to the B6 haplotype. In addition, we show that 129-strain NK cells possess comparable Nkrp1 and Clr transcript expression, and characterize several NKR-P1:Clr interactions that are functionally conserved between the B6 and 129 strains, including documented and novel receptor-ligand pairs. Thus, despite significant allelic polymorphism observed in the Nkrp1-Clr region, the overall genetic organization and functional repertoire appear to be conserved among mouse strains, in contrast to the striking variation observed in the corresponding Ly49 region. These data extend our knowledge of the complex genetically linked Nkrp1-Clr NK recognition system in mice.

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Paired opposing leukocyte receptors recognizing rapidly evolving ligands are subject to homogenization of their ligand binding domains

et al. 2011

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Some leukocyte receptors come in groups of two or more where the partners share ligand(s) but transmit opposite signals. Some of the ligands, such as MHC class I, are fast evolving, raising the problem of how paired opposing receptors manage to change in step with respect to ligand binding properties and at the same time conserve opposite signaling functions. An example is the KLRC (NKG2) family, where opposing variants have been conserved in both rodents and primates. Phylogenetic analyses of the KLRC receptors within and between the two orders show that the opposing partners have been subject to post-speciation gene homogenization restricted mainly to the parts of the genes that encode the ligand binding domains. Concerted evolution similarly restricted is demonstrated also for the KLRI, KLRB (NKR-P1), KLRA (Ly49), and PIR receptor families. We propose the term merohomogenization for this phenomenon and discuss its significance for the evolution of immune receptors.

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Phylogenetic and functional conservation of the NKR-P1F and NKR-P1G receptors in rat and mouse

Cited by 28 publications

References 18 publications

Functional characterization of a conserved pair of NKR‐P1 receptors expressed by NK cells and T lymphocytes in liver and gut

Functional characterization of a conserved pair of NKR‐P1 receptors expressed by NK cells and T lymphocytes in liver and gut

Analysis of the mouse 129-strain Nkrp1-Clr gene cluster reveals conservation of genomic organization and functional receptor–ligand interactions despite significant allelic polymorphism

Paired opposing leukocyte receptors recognizing rapidly evolving ligands are subject to homogenization of their ligand binding domains

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