ULBP4 is a novel ligand for human NKG2D.
The ULBPs are a family of MHC class I-related molecules. We have previously shown that ULBPs 1, 2, and 3 are functional ligands of the NKG2D/DAP10 receptor complex on human natural killer (NK) cells. Here, we describe a new member of the ULBP family, ULBP4, which contains predicted transmembrane and cytoplasmic domains, unlike the other ULBPs, which are GPI-linked proteins. Transduction of ULBP4 into EL4 cells confers the ability to bind recombinant NKG2D and mediates increased cytotoxic activity by human NK cells, consistent with the role of ULBPs as ligands for the NKG2D/DAP10 activating receptors. Tissue expression of ULBP4 differs from other members of the family, in that it is expressed predominantly in the skin.
Amgen, 51 University St, Seattle, WA 98101, USA.
N Jan
NJ
Chalupny
Claire L
CL
Sutherland
William A
WA
Lawrence
Annie
A
Rein-Weston
David
D
Cosman
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D006023:Glycoproteins / Q000378:metabolism; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D008024:Ligands; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic / Q000737:chemistry / Q000378:metabolism*; D055607:Receptors, Natural Killer Cell; D016415:Sequence Alignment; D012867:Skin / Q000378:metabolism; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured; D014764:Viral Proteins / Q000378:metabolism
D002352:Carrier Proteins; D006023:Glycoproteins; D017261:Glycosylphosphatidylinositols; D015395:Histocompatibility Antigens Class I; C527085:KLRK1 protein, human; C527086:Klrk1 protein, mouse; D008024:Ligands; D008565:Membrane Proteins; D055655:NK Cell Lectin-Like Receptor Subfamily K; C488760:RAET1E protein, human; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D014764:Viral Proteins