Synonyms
Historical Background
NK cell function is finely regulated by a series of inhibitory or activating receptors. The inhibitory receptors, specific for major histocompatibility complex (MHC) class I molecules, allow NK cells to discriminate between normal cells and cells that have lost the expression of MHC class I (e.g., tumor cells). In the absence of sufficient signaling by their HLA class I-specific inhibitory receptors, human natural killer (NK) cells become activated and display potent cytotoxicity against cells that are HLA class I negative. This indicates that the NK receptors responsible for the induction of cytotoxicity recognize ligands on target cells different from HLA class I molecules. These receptors have been termed natural cytotoxicity receptors (NCR) and include NKp46, together with NKp44 and NKp30 (Bottino et al. 2000). A direct correlation exists between the surface density of NCR and the ability of NK cells to kill various target cells (Sivori et al. 1999...
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Arnon TI, Achdout H, Lieberman N, Gazit R, Gonen-Gross T, Katz G, et al. The mechanisms controlling the recognition of tumor- and virus-infected cells by NKp46. Blood. 2004;103:664–72. https://doi.org/10.1182/blood-2003-05-1716.
Bensussan A, Remtoula N, Sivori S, Bagot M, Moretta A, Marie-Cardine A. Expression and function of the natural cytotoxicity receptor NKp46 on circulating malignant CD4+ T lymphocytes of Sézary syndrome patients. J Invest Dermatol. 2011;131:969–76. https://doi.org/10.1038/jid.2010.404.
Biassoni R. Natural killer cell receptors. Adv Exp Med Biol. 2008;640:35–52. https://doi.org/10.1007/978-0-387-09789-3_4.
Björkström NK, Riese P, Heuts F, Andersson S, Fauriat C, Ivarsson MA, et al. Expression patterns of NKG2A, KIR, and CD57 define a process of CD56dim NK-cell differentiation uncoupled from NK-cell education. Blood. 2010;116:3853–64. https://doi.org/10.1182/blood-2010-04-281675.
Bloushtain N, Qimron U, Bar-Ilan A, Hershkovitz O, Gazit R, Fima E, et al. Membrane-associated heparan sulfate proteoglycans are involved in the recognition of cellular targets by NKp30 and NKp46. J Immunol. 2004;173:2392–401.
Bottino C, Biassoni R, Millo R, Moretta L, Moretta A. The human natural cytotoxicity receptors (NCR) that induce HLA class I-independent NK cell triggering. Hum Immunol. 2000;61:1–6.
Capila I, Linhardt RJ. Heparin-protein interactions. Angew Chem Int Ed Eng. 2002;41:391–412. https://doi.org/10.1002/1521-3773(20020201)41:3<390::AID-ANIE390>3.0.CO;2-B.
Cella M, Fuchs A, Vermi W, Facchetti F, Otero K, Lennerz JK, et al. A human natural killer cell subset provides an innate source of IL-22 for mucosal immunity. Nature. 2009;457:722–5. https://doi.org/10.1038/nature07537.
Diefenbach A, Colonna M, Koyasu S. Development, differentiation, and diversity of innate lymphoid cells. Immunity. 2014;41:354–65. https://doi.org/10.1016/j.immuni.2014.09.005.
Dudakov JA, Hanash AM, van den Brink MR. Interleukin-22: immunobiology and pathology. Annu Rev Immunol. 2015;33:747–85. https://doi.org/10.1146/annurev-immunol-032414-112123.
Garg A, Barnes PF, Porgador A, Roy S, Wu S, Nanda JS, et al. Vimentin expressed on Mycobacterium tuberculosis-infected human monocytes is involved in binding to the NKp46 receptor. J Immunol. 2006;177:6192–8.
Gazit R, Gruda R, Elboim M, Arnon TI, Katz G, Achdout H, et al. Lethal influenza infection in the absence of the natural killer cell receptor gene Ncr1. Nat Immunol. 2006;7:517–23. https://doi.org/10.1038/ni1322.
Glatzer T, Killig M, Meisig J, Ommert I, Luetke-Eversloh M, Babic M, et al. RORgammat(+) innate lymphoid cells acquire a proinflammatory program upon engagement of the activating receptor NKp44. Immunity. 2013;38:1223–35. https://doi.org/10.1016/j.immuni.2013.05.013.
Hoorweg K, Peters CP, Cornelissen F, Aparicio-Domingo P, Papazian N, Kazemier G, et al. Functional differences between human NKp44(−) and NKp44(+) RORC(+) innate lymphoid cells. Front Immunol. 2012;3:72. https://doi.org/10.3389/fimmu.2012.00072.
Kelley J, Walter L, Trowsdale J. Comparative genomics of natural killer cell receptor gene clusters. PLoS Genet. 2005;1:129–39. https://doi.org/10.1371/journal.pgen.0010027.
Killig M, Glatzer T, Romagnani C. Recognition strategies of group 3 innate lymphoid cells. Front Immunol. 2014;5:142. https://doi.org/10.3389/fimmu.2014.00142.
Lopez-Vergès S, Milush JM, Pandey S, York VA, Arakawa-Hoyt J, Pircher H, et al. CD57 defines a functionally distinct population of mature NK cells in the human CD56dimCD16+ NK-cell subset. Blood. 2010;116:3865–74. https://doi.org/10.1182/blood-2010-04-282301.
Mandelboim O, Lieberman N, Lev M, Paul L, Arnon TI, Bushkin Y, et al. Recognition of haemagglutinins on virus-infected cells by NKp46 activates lysis by human NK cells. Nature. 2001;409:1055–60. https://doi.org/10.1038/35059110.
Meresse B, Curran SA, Ciszewski C, Orbelyan G, Setty M, Bhagat G, et al. Reprogramming of CTLs into natural killer-like cells in celiac disease. J Exp Med. 2006;203:1343–55. https://doi.org/10.1084/jem.20060028.
Montaldo E, Vacca P, Moretta L, Mingari MC. Development of human natural killer cells and other innate lymphoid cells. Semin Immunol. 2014;26:107–13. https://doi.org/10.1016/j.smim.2014.01.006.
Moretta A, Bottino C, Vitale M, Pende D, Cantoni C, Mingari MC, et al. Activating receptors and coreceptors involved in human natural killer cell-mediated cytolysis. Annu Rev Immunol. 2001;19:197–223. https://doi.org/10.1146/annurev.immunol.19.1.197.
Muntasell A, Vilches C, Angulo A, López-Botet M. Adaptive reconfiguration of the human NK-cell compartment in response to cytomegalovirus: a different perspective of the host-pathogen interaction. Eur J Immunol. 2013;43:1133–41. https://doi.org/10.1002/eji.201243117.
Pesce S, Greppi M, Tabellini G, Rampinelli F, Parolini S, Olive D, et al. Identification of a subset of human natural killer cells expressing high levels of programmed death 1: a phenotypic and functional characterization. J Allergy Clin Immunol. 2016; pii: S0091-6749(16)30360-8. https://doi.org/10.1016/j.jaci.2016.04.025.
Pessino A, Sivori S, Bottino C, Malaspina A, Morelli L, Moretta L, et al. Molecular cloning of NKp46: a novel member of the immunoglobulin superfamily involved in triggering of natural cytotoxicity. J Exp Med. 1998;188:953–60.
Ponassi M, Cantoni C, Biassoni R, Conte R, Spallarossa A, Moretta A, et al. Expression and crystallographic characterization of the extracellular domain of human natural killer cell triggering receptor NKp46. Acta Crystallogr D Biol Crystallogr. 2003;59:2259–61. https://doi.org/10.1107/S090744490301895X.
Rankin LC, Girard-Madoux MJ, Seillet C, Mielke LA, Kerdiles Y, Fenis A, et al. Complementarity and redundancy of IL-22-producing innate lymphoid cells. Nat Immunol. 2016;17:179–86. https://doi.org/10.1038/ni.3332.
Rölle A, Brodin P. Immune adaptation to environmental influence: the case of NK cells and HCMV. Trends Immunol. 2016;37:233–43. https://doi.org/10.1016/j.it.2016.01.005.
Satoh-Takayama N, Vosshenrich CA, Lesjean-Pottier S, Sawa S, Lochner M, Rattis F, et al. Microbial flora drives interleukin 22 production in intestinal NKp46+ cells that provide innate mucosal immune defense. Immunity. 2008;29:958–70. https://doi.org/10.1016/j.immuni.2008.11.001.
Seillet C, Belz GT, Huntington ND. Development, homeostasis, and heterogeneity of NK cells and ILC1. Curr Top Microbiol Immunol. 2016;395:37–61. https://doi.org/10.1007/82_2015_474.
Sivori S, Vitale M, Morelli L, Sanseverino L, Augugliaro R, Bottino C, et al. p46, a novel natural killer cell-specific surface molecule that mediates cell activation. J Exp Med. 1997;186:1129–36.
Sivori S, Pende D, Bottino C, Marcenaro E, Pessino A, Biassoni R, et al. NKp46 is the major triggering receptor involved in the natural cytotoxicity of fresh or cultured human NK cells. Correlation between surface density of NKp46 and natural cytotoxicity against autologous, allogeneic or xenogeneic target cells. Eur J Immunol. 1999;29:1656–66.
Spits H, Artis D, Colonna M, Diefenbach A, Di Santo JP, Eberl G, et al. Innate lymphoid cells: a proposal for uniform nomenclature. Nat Rev Immunol. 2013;13:145–9. https://doi.org/10.1038/nri3365.
Vacca P, Montaldo E, Croxatto D, Moretta F, Bertaina A, Vitale C, et al. NK cells and other innate lymphoid cells in hematopoietic stem cell transplantation. Front Immunol. 2016;7:188. https://doi.org/10.3389/fimmu.2016.00188.
Vivier E, Spits H, Cupedo T. Interleukin-22-producing innate immune cells: new players in mucosal immunity and tissue repair? Nat Rev Immunol. 2009;9:229–34. https://doi.org/10.1038/nri2522.
Warren HS, Jones AL, Freeman C, Bettadapura J, Parish CR. Evidence that the cellular ligand for the human NK cell activation receptor NKp30 is not a heparan sulfate glycosaminoglycan. J Immunol. 2005;175:207–12.
Zilka A, Landau G, Hershkovitz O, Bloushtain N, Bar-Ilan A, Benchetrit F, et al. Characterization of the heparin/heparan sulfate binding site of the natural cytotoxicity receptor NKp46. Biochemistry. 2005;44:14477–85. https://doi.org/10.1021/bi051241s.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer International Publishing AG
About this entry
Cite this entry
Sivori, S. (2018). NKp46. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_564
Download citation
DOI: https://doi.org/10.1007/978-3-319-67199-4_564
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-67198-7
Online ISBN: 978-3-319-67199-4
eBook Packages: Biomedical and Life SciencesReference Module Biomedical and Life Sciences