Ligands for the murine NKG2D receptor: expression by tumor cells and activation of NK cells and macrophages

Nat Immunol. 2000 Aug;1(2):119-26. doi: 10.1038/77793.


Natural killer (NK) cells attack tumor and infected cells, but the receptors and ligands that stimulate them are poorly understood. Here we report the expression cloning of two murine ligands for the lectin-like receptor NKG2D. The two ligands, H-60 and Rae1 beta, are distant relatives of major histocompatibility complex class I molecules. NKG2D ligands are not expressed by most normal cells but are up-regulated on numerous tumor cells. We show that mouse NKG2D is expressed by NK cells, activated CD8+ T cells and activated macrophages. Expression of either NKG2D ligand by target cells triggers NK cell cytotoxicity and interferon-gamma secretion by NK cells, as well as nitric oxide release and tumor necrosis factor alpha transcription by macrophages. Thus, through their interaction with NKG2D, H-60 and Rae1 beta are newly identified potent stimulators of innate immunity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CHO Cells
  • COS Cells
  • Chlorocebus aethiops
  • Cloning, Molecular
  • Cricetinae
  • Humans
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Ligands
  • Lymphocyte Activation
  • Macrophage Activation
  • Macrophages, Peritoneal / immunology*
  • Macrophages, Peritoneal / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Minor Histocompatibility Antigens / genetics
  • Minor Histocompatibility Antigens / immunology*
  • NK Cell Lectin-Like Receptor Subfamily K
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism*
  • Receptors, Natural Killer Cell
  • Tumor Cells, Cultured


  • KLRK1 protein, human
  • Klrk1 protein, mouse
  • Ligands
  • Membrane Proteins
  • Minor Histocompatibility Antigens
  • NK Cell Lectin-Like Receptor Subfamily K
  • Raet1a protein, mouse
  • Receptors, Immunologic
  • Receptors, Natural Killer Cell
  • minor H antigen H60