Association of DAP12 with activating CD94/NKG2C NK cell receptors.
While the inhibitory NK cell receptors for MHC class I express immunoreceptor tyrosine-based inhibitory motifs that recruit intracellular tyrosine phosphatases and prevent NK cell effector function, the activating NK cell receptors lack intrinsic sequences required for cellular stimulation. CD94/NKG2C, an activating NK cell receptor of the C-type lectin superfamily that binds to HLA-E, noncovalently associates with DAP12, a membrane receptor containing an immunoreceptor tyrosine-based activating motif. Efficient expression of CD94/NKG2C on the cell surface requires the presence of DAP12, and charged residues in the transmembrane domains of DAP12 and NKG2C are necessary for this interaction. These results provide a molecular basis for the assembly of NK cell receptors for MHC class I involved in cellular activation and inhibition.
Lanier
L L
LL
DNAX Research Institute of Molecular and Cellular Biology, Immunobiology Department, Palo Alto, California 94304, USA. lanier@dnax.org
Corliss
B
B
Wu
J
J
Phillips
J H
JH
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000276:immunology*; D002460:Cell Line; D006680:HLA Antigens / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D037102:Lectins / Q000276:immunology; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000276:immunology*; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011971:Receptors, Immunologic / Q000276:immunology*; D014162:Transfection; D000097625:HLA-E Antigens
D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D037102:Lectins; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011971:Receptors, Immunologic; D000097625:HLA-E Antigens; C497869:KLRD1 protein, human; C110546:TYROBP protein, human