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

Eur J Immunol. 2001 Jan;31(1):233-42. doi: 10.1002/1521-4141(200101)31:1<233::AID-IMMU233>3.0.CO;2-4.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amino Acid Sequence
  • Animals
  • Antigens, Surface / analysis
  • Calcium / metabolism
  • Cell Line
  • Cloning, Molecular
  • Cytotoxicity, Immunologic
  • Female
  • Humans
  • Killer Cells, Natural / chemistry*
  • Lymphocyte Activation
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Middle Aged
  • Molecular Sequence Data
  • Receptors, Immunologic / analysis*
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / physiology


  • Antigens, Surface
  • Receptors, Immunologic
  • Calcium

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