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

Simona Sivori, Daniela Pende, Cristina Bottino, Emanuela Marcenaro, Anna Pessino, Roberto Biassoni, Lorenzo Moretta, Alessandro Moretta

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Abstract

NKp46 is a novel triggering receptor expressed by all human NK cells that is involved in natural cytotoxicity. In this study we show that the surface density of NKp46 may vary in different NK cells and that a precise correlation exists between the NKp46 phenotype of NK clones and their natural cytotoxicity against HLA-class I-unprotected allogeneic or xenogeneic cells. Thus, NKp46(bright) clones efficiently lysed human and murine tumor cells while NKp46(dull) clones were poorly cytolytic against both types of target cells. We also show that the NKp46 phenotype of NK clones correlates with their ability to lyse HLA-class I-unprotected autologous cells. Finally, NKp46 was found to be deeply involved in the natural cytotoxicity mediated by freshly derived NK cells. This was indicated both by the inhibition of cytolysis after monoclonal antibody-mediated masking of NKp46 and by the correlation existing between the natural cytotoxicity of fresh NK cells derived from different donors and their NKp46 phenotype. In conclusion, these studies strongly support the concept that NKp46 plays a central role in the physiological triggering of NK cells and, as a consequence (in concert with killer inhibitory receptors), in the NK-mediated clearance of abnormal cells expressing inadequate amounts of HLA-class I molecules.

Original languageEnglish
Pages (from-to)1656-1666
Number of pages11
JournalEuropean Journal of Immunology
Volume29
Issue number5
DOIs
Publication statusPublished - 1999

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Natural Killer Cells
Clone Cells
Phenotype
KIR Receptors
Monoclonal Antibodies
Neoplasms

Keywords

  • Activating receptor
  • Natural cytotoxicity
  • NK cell

ASJC Scopus subject areas

  • Immunology

Cite this

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title = "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",
abstract = "NKp46 is a novel triggering receptor expressed by all human NK cells that is involved in natural cytotoxicity. In this study we show that the surface density of NKp46 may vary in different NK cells and that a precise correlation exists between the NKp46 phenotype of NK clones and their natural cytotoxicity against HLA-class I-unprotected allogeneic or xenogeneic cells. Thus, NKp46(bright) clones efficiently lysed human and murine tumor cells while NKp46(dull) clones were poorly cytolytic against both types of target cells. We also show that the NKp46 phenotype of NK clones correlates with their ability to lyse HLA-class I-unprotected autologous cells. Finally, NKp46 was found to be deeply involved in the natural cytotoxicity mediated by freshly derived NK cells. This was indicated both by the inhibition of cytolysis after monoclonal antibody-mediated masking of NKp46 and by the correlation existing between the natural cytotoxicity of fresh NK cells derived from different donors and their NKp46 phenotype. In conclusion, these studies strongly support the concept that NKp46 plays a central role in the physiological triggering of NK cells and, as a consequence (in concert with killer inhibitory receptors), in the NK-mediated clearance of abnormal cells expressing inadequate amounts of HLA-class I molecules.",
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author = "Simona Sivori and Daniela Pende and Cristina Bottino and Emanuela Marcenaro and Anna Pessino and Roberto Biassoni and Lorenzo Moretta and Alessandro Moretta",
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AU - Sivori, Simona

AU - Pende, Daniela

AU - Bottino, Cristina

AU - Marcenaro, Emanuela

AU - Pessino, Anna

AU - Biassoni, Roberto

AU - Moretta, Lorenzo

AU - Moretta, Alessandro

PY - 1999

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