CD69-triggered ERK activation and functions are negatively regulated by CD94 / NKG2-A inhibitory receptor

Eur J Immunol. 2000 Feb;30(2):644-51. doi: 10.1002/1521-4141(200002)30:2<644::AID-IMMU644>3.0.CO;2-H.


CD69 represents a functional triggering molecule on activated NK and T cells, capable of inducing cytotoxic activity and costimulating cytokine production. It belongs to the C-lectin type superfamily, and its gene maps in the NK gene complex, close to other genes coding for NK receptors. CD94 / NKG2-A complex is the inhibitory receptor for the non classical MHC class I molecule HLA-E on human NK cells. To investigate CD69-initiated signal transduction pathways, and to evaluate CD94 / NKG2-A interference on CD69 triggering ability, we have generated transfectants expressing both receptors in the RBL cell line. Here we report that CD69 engagement leads to the activation of extracellular signal-regulated kinase (ERK) enzymes belonging to the MAPK family, and that this event is required for CD69-mediated cell degranulation. Moreover, we show that the co-engagement of CD94 / NKG2-A inhibitory receptor effectively suppresses both CD69-triggered cell degranulation in RBL transfectants, through the inhibition of ERK activation, and CD69-induced cytotoxicity in human NK cells. Thus, here we provide new information on the molecular mechanisms initiated by CD69 activation receptor, and show that CD69-initiated signaling pathways and functional activity are negatively regulated by CD94 / NKG2-A inhibitory complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / immunology*
  • Antigens, Differentiation, T-Lymphocyte / immunology*
  • Cell Line
  • Humans
  • Killer Cells, Natural / immunology*
  • Lectins, C-Type*
  • Lymphocyte Activation*
  • Membrane Glycoproteins / immunology*
  • Mice
  • Mitogen-Activated Protein Kinases / immunology
  • NK Cell Lectin-Like Receptor Subfamily C
  • NK Cell Lectin-Like Receptor Subfamily D
  • Receptor Cross-Talk / immunology
  • Receptors, Immunologic / immunology*
  • Receptors, Natural Killer Cell
  • Signal Transduction / immunology*


  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD69 antigen
  • KLRC1 protein, human
  • KLRD1 protein, human
  • Klrc1 protein, mouse
  • Klrd1 protein, mouse
  • Lectins, C-Type
  • Membrane Glycoproteins
  • NK Cell Lectin-Like Receptor Subfamily C
  • NK Cell Lectin-Like Receptor Subfamily D
  • Receptors, Immunologic
  • Receptors, Natural Killer Cell
  • Mitogen-Activated Protein Kinases