Identification of NKp80, a novel triggering molecule expressed by human NK cells

Massimo Vitale, Michela Falco, Roberta Castriconi, Silvia Parolini, Renato Zambello, Gianpietro Semenzato, Roberto Biassoni, Cristina Bottino, Lorenzo Moretta, Alessandro Moretta

Research output: Contribution to journalArticlepeer-review

Abstract

The ability of NK cells to kill a wide range of tumor or virally infected target cells as well as normal allogeneic T cell blasts appears to depend upon the concerted action of multiple triggering NK receptors. In this study, using two specific monoclonal antibodies [(mAb) MA152 and LAP171], we identified a triggering NK receptor expressed at the cell surface as a dimer of approximately 80 kDa (NKp80). NKp80 is expressed by virtually all fresh or activated NK cells and by a minor subset of T cells characterized by the CD56 surface antigen. NKp80 surface expression was also detected in all CD3-and in 6/10 CD3+large granular lymphocyte expansions derived from patients with lymphoproliferative disease of granular lymphocytes. In polyclonal NK cells, mAb-mediated cross-linking of NKp80 resulted in induction of cytolytic activity and Ca2+mobilization. A marked heterogeneity existed in the magnitude of the cytolytic responses of different NK cell clones to anti-NKp80 mAb. This heterogeneity correlated with the surface density of NKp46 molecules expressed by different NK clones. The mAb-mediated masking of NKp80 led to a partial inhibition of the NK-mediated lysis of appropriate allogeneic phytohemagglutinin-induced T cell blasts, while it had no effect on the lysis of different tumor target cells, including T cell leukemia cells. These data suggest that NKp80 recognizes a ligand on normal T cells that may be down-regulated during tumor transformation. Molecular cloning of the cDNA coding for NKp80 revealed a type II transmembrane molecule of 231 amino acids identical to the putative protein encoded by a recently identified cDNA termed KLRF1.

Original languageEnglish
Pages (from-to)233-242
Number of pages10
JournalEuropean Journal of Immunology
Volume31
Issue number1
DOIs
Publication statusPublished - 2001

Keywords

  • Activating receptor
  • C-type lectin molecule
  • Cell-mediated cytotoxicity
  • Lymphoproliferative disease of granular lymphocytes
  • NK cell

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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