NCR

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Contents

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Introduction

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Human

Natural cytotoxicity receptors NKp30, NKp44, NKp46 are three of the most important triggering receptors found an NK cells. NCRs are expected to directly recognize molecules on tumor cells, thus activating NK cells and lysis tumors. Poggi et al (2005 [1]) report that NCRs not only are responsible for NK cell activation but are also envolved in NK cell suicide: Crosslinking of NKp30 and NKp46 (to a lesser extent NKp44) induced upregulation of FasL mRNA in NK cells, release of FasL protein to the culture supernatant and percentage of apoptotic cells (by Annexin V staining). Soluble anti-NCR antibodies did not induce apoptosis.

A cellular ligand for NKp30 has been identified by von Strandmann et al. (ASH 2006): HLA-B-Associated Transkript 3 (BAT3). BAT3 exhibits a novel mechanism by which a nuclear protein activates NK cells via NKp30-engagement after its release to the cell-surface and the cell environment.

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Rat

NKp30 has also been identified in rats. RNKp30 is a glycosylated Natural Killer cell receptor and has limited polymorphism (5 SNPs identified; Hsieh, Transplantation 2004). Polyclonal (CA680, CA1071) and monoclonal (Stanford Docket S04-250) antibodies against rNKp30 have been generated.

A homologue to human NKp46 (termed RAR-1) has been identified in rats (Falco, 1999 [2]). Similar to humans, rNKp46 is an activating receptor associated with CD3{zeta} (Westgaard, 2004 [3]).

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Mouse

MAR-1 has been described as the murine homologue to human NKp46 (Biassoni et al., Eur.J.Immunol., 1999 [4])

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Cattle

NKp46 has also been identified as NK cell specific marker in cattle (Storset, Eur.J.Immunol. 2004 [5])

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Family members

Cluster of differentiation numbers assigned in 8th HLDA workshop:

  • CD335 - NKp46 - NCR1
  • CD336 - NKp44 - NCR2
  • CD337 - NKp30 - NCR3
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Ligands

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Cellular ligands

  • NKp46
    • heparan sulfate moieties of membranal heparan sulfate proteoglycans (HSPGs) (region containing the basic amino acids K133, R136, H139, R142, and K146) (Zilka, 2005 [6])
  • NKp30
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Antibodies

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References

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2007

Ho JW, Hershkovitz O, Peiris M, Zilka A, Bar-Ilan A, Nal B, Chu K, Kudelko M, Kam YW, Achdout H, Mandelboim M, Altmeyer R, Mandelboim O, Bruzzone R, Porgador A.
H5-type Influenza Hemagglutinin is Functionally Recognized by the Natural Killer Activating Receptor, NKp44.
J Virol. 2007 Dec 12;. Epub, PMID:18077718

Hershkovitz O, Jarahian M, Zilka A, Bar-Ilan A, Landau G, Jivov S, Tekoah Y, Glicklis R, Gallagher JT, Hoffmann SC, Zer H, Mandelboim O, Watzl C, Momburg F, Porgador A.
Altered Glycosylation of Recombinant NKp30 Hampers Binding to Heparan Sulfate: a Lesson for the Use of Recombinant Immuno-Receptors as an Immunological Tool.
Glycobiology. 2007 Nov 15;. Epub, PMID:18006589

Poggi A, Prevosto C, Zancolli M, Canevali P, Musso A, Zocchi MR.
NKG2D and Natural Cytotoxicity Receptors Are Involved in Natural Killer Cell Interaction with Self-Antigen Presenting Cells and Stromal Cells.
Ann N Y Acad Sci. 2007 Sep;1109:47-57., PMID:17785290

Rutjens E, Mazza S, Biassoni R, Koopman G, Radic L, Fogli M, Costa P, Mingari MC, Moretta L, Heeney J, De Maria A.
Differential NKp30 inducibility in chimpanzee NK cells and conserved NK cell phenotype and function in long-term HIV-1-infected animals.
J Immunol. 2007 Feb 1;178(3):1702-12. Erratum in: J Immunol. 2007 Jul 15;179(2):1389., PMID:17237420 (Free Full Text)

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2006

Tumor Cell-Derived HLA-B-Associated Transkript 3 (BAT3) Is a Ligand for NKp30 and Activates NK Cells.
Elke Pogge von Strandmann, Venkateswara R. Simhadri, Bastian von Tresckow, Stefanie Sasse, Katrin S. Reiners, Hinrich P. Hansen, Achim Rothe, Peter Borchmann, Peter J. McKinnon, Michael Hallek, and Andreas Engert
Blood (ASH Annual Meeting Abstracts). 2006; 108(11): p. 643

Della Chiesa M, Carlomagno S, Frumento G, Balsamo M, Cantoni C, Conte R, Moretta L, Moretta A, Vitale M.
The tryptophan catabolite L-kynurenine inhibits the surface expression of NKp46 and NKG2D activating receptors and regulates NK cell function.
Blood. 2006 Aug 10;. Epub, PMID:16902152

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2005

Poggi A, Prevosto C, Massaro AM, Negrini S, Urbani S, Pierri I, Saccardi R, Gobbi M, Zocchi MR.
Interaction between human NK cells and bone marrow stromal cells induces NK cell triggering: role of NKp30 and NKG2D receptors.
J Immunol. 2005 Nov 15;175(10):6352-60., PMID:16272287 NKref521

Zilka A, Landau G, Hershkovitz O, Bloushtain N, Bar-Ilan A, Benchetrit F, Fima E, van Kuppevelt TH, Gallagher JT, Elgavish S, Porgador A.
Characterization of the Heparin/Heparan Sulfate Binding Site of the Natural Cytotoxicity Receptor NKp46.
Biochemistry. 2005 Nov 8;44(44):14477-14485. PMID: 16262248

Paradoxical inhibition of human natural interferon-producing cells by the activating receptor NKp44
Anja Fuchs, Marina Cella, Takayuki Kondo, and Marco Colonna
Blood published 7 June 2005, 10.1182/blood-2004-12-4802 NKref0445

Poggi A, Massaro AM, Negrini S, Contini P, Zocchi MR.
Tumor-induced apoptosis of human IL-2-activated NK cells: role of natural cytotoxicity receptors.
J Immunol. 2005 Mar 1;174(5):2653-60. PMID: 15728472

Hollyoake M, Campbell RD, Aguado B.
NKp30 (NCR3) is a pseudogene in 12 inbred and wild mouse strains, but an expressed gene in Mus caroli.
Mol Biol Evol. 2005 Aug;22(8):1661-72. Epub 2005 May 4. PMID: 15872155

Vitale M, Della Chiesa M, Carlomagno S, Pende D, Aricò M, Moretta L, Moretta A.
NK-dependent DC maturation is mediated by TNFalpha and IFNgamma released upon engagement of the NKp30 triggering receptor.
Blood. 2005 Jul 15;106(2):566-71. Epub 2005 Mar 22., [[PMID:15784725] (Free Full Text)

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2004

Westgaard IH, Berg SF, Vaage JT, Wang LL, Yokoyama WM, Dissen E, Fossum S
Rat NKp46 activates natural killer cell cytotoxicity and is associated with Fc{varepsilon}RI{gamma} and CD3{zeta}
J Leukoc Biol. 2004 Sep 8;. Epub PMID: 15356098

Arnon TI, Achdout H, Lieberman N, Gazit R, Gonen-Gross T, Katz G, Bar-Ilan A, Bloushtain N, Lev M, Joseph A, Kedar E, Porgador A, Mandelboim O.
The mechanisms controlling the recognition of tumor- and virus-infected cells by NKp46.
Blood. 2004 Jan 15;103(2):664-72. Epub 2003 Sep 22. PMID: 14504081

Andre P, Castriconi R, Espeli M, Anfossi N, Juarez T, Hue S, Conway H, Romagne F, Dondero A, Nanni M, Caillat-Zucman S, Raulet DH, Bottino C, Vivier E, Moretta A, Paul P.
Comparative analysis of human NK cell activation induced by NKG2D and natural cytotoxicity receptors.
Eur J Immunol. 2004 Apr;34(4):961-71. PMID: 15048706 NKref0291

Storset AK, Kulberg S, Berg I, Boysen P, Hope JC, Dissen E.
NKp46 defines a subset of bovine leukocytes with natural killer cell characteristics.
Eur J Immunol. 2004 Mar;34(3):669-76. PMID: 14991596 NKref0280

Hsieh CL, Ogura Y, Obara H, Ali UA, Rodriguez GM, Nepomuceno RR, Martinez OM, Krams SM.
Identification, cloning, and characterization of a novel rat natural killer receptor, RNKP30: a molecule expressed in liver allografts.
Transplantation. 2004 Jan 15;77(1):121-8. PMID: 14724446

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2003

De Maria A, Fogli M, Costa P, Murdaca G, Puppo F, Mavilio D, Moretta A, Moretta L.
The impaired NK cell cytolytic function in viremic HIV-1 infection is associated with a reduced surface expression of natural cytotoxicity receptors (NKp46, NKp30 and NKp44).
Eur J Immunol. 2003 Sep;33(9):2410-8. PMID: 12938217 NKref0300

Marcenaro E, Augugliaro R, Falco M, Castriconi R, Parolini S, Sivori S, Romeo E, Millo R, Moretta L, Bottino C, Moretta A.
CD59 is physically and functionally associated with natural cytotoxicity receptors and activates human NK cell-mediated cytotoxicity.
Eur J Immunol. 2003 Dec;33(12):3367-76. PMID: 14635045

Augugliaro R, Parolini S, Castriconi R, Marcenaro E, Cantoni C, Nanni M, Moretta L, Moretta A, Bottino C.
Selective cross-talk among natural cytotoxicity receptors in human natural killer cells.
Eur J Immunol. 2003 May;33(5):1235-41. PMID: 12731048

Backman-Petersson E, Miller JR, Hollyoake M, Aguado B, Butcher GW.
Molecular characterization of the novel rat NK receptor 1C7.
Eur J Immunol. 2003 Feb;33(2):342-51. PMID: 12548565

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2002 and earlier

Ferlazzo G, Tsang ML, Moretta L, Melioli G, Steinman RM, Münz C.
Human dendritic cells activate resting natural killer (NK) cells and are recognized via the NKp30 receptor by activated NK cells.
J Exp Med. 2002 Feb 4;195(3):343-51., PMID:11828009 (Free Full Text)

Arnon TI, Lev M, Katz G, Chernobrov Y, Porgador A, Mandelboim O.
Recognition of viral hemagglutinins by NKp44 but not by NKp30.
Eur J Immunol. 2001 Sep;31(9):2680-9. PMID: 11536166

Pende D, Cantoni C, Rivera P, Vitale M, Castriconi R, Marcenaro S, Nanni M, Biassoni R, Bottino C, Moretta A, Moretta L.
Role of NKG2D in tumor cell lysis mediated by human NK cells: cooperation with natural cytotoxicity receptors and capability of recognizing tumors of nonepithelial origin.
Eur J Immunol. 2001 Apr;31(4):1076-86., PMID:11298332

Biassoni R, Pessino A, Bottino C, Pende D, Moretta L, Moretta A.
The murine homologue of the human NKp46, a triggering receptor involved in the induction of natural cytotoxicity.
Eur J Immunol. 1999 Mar;29(3):1014-20. PMID: 10092106 (MAR-1)

Falco M, Cantoni C, Bottino C, Moretta A, Biassoni R.
Identification of the rat homologue of the human NKp46 triggering receptor.
Immunol Lett. 1999 Jun 1;68(2-3):411-4. No abstract available. PMID: 10424451 (RAR-1)

Pessino A, Sivori S, Bottino C, Malaspina A, Morelli L, Moretta L, Biassoni R, Moretta A.
Molecular cloning of NKp46: a novel member of the immunoglobulin superfamily involved in triggering of natural cytotoxicity.
J Exp Med. 1998 Sep 7;188(5):953-60. PMID: 9730896

Sivori S, Vitale M, Morelli L, Sanseverino L, Augugliaro R, Bottino C, Moretta L, Moretta A.
p46, a novel natural killer cell-specific surface molecule that mediates cell activation.
J Exp Med. 1997 Oct 6;186(7):1129-36., PMID:9314561 (Free Full Text, First publication of NKp46 molecule; Citation Map)

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