CDB15:0001285 RAET1E — KLRK1
Experimentally validated in Human; Orthology-inferred in Rat, Zebrafish, Macaque, Pig, Cow, Chimp, Marmoset, Sheep
Title
Journal:; Year Published:
Abstract
ULBP4 is a novel ligand for human NKG2D.
Biochemical and biophysical research communications, 2003; PubMed, Homo sapiens RAET1E — Homo sapiens KLRK1
ABSTRACT: 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.
Letal, A tumor-associated NKG2D immunoreceptor ligand, induces activation and expansion of effector immune cells.
Cancer biology & therapy, 2003; PubMed, Homo sapiens RAET1E — Homo sapiens KLRK1
ABSTRACT: NKG2D serves as one of the most potent activating receptors for effector lymphocytes. in peripheral tissues. Here we report the characterization of Letal, the first human trans-membrane NKG2D ligand lacking an immunoglobulin-like alpha-3 ectodomain. Letal is constitutively expressed by a variety of normal tissues, and is upregulated in tumor cells of different origins. Unlike other NKG2D ligands, Letal mRNA expression progressively decreased after treatment of tumor cells with retinoic acid. Simultaneous T-cell receptor activation and engagement of Letal stimulated proliferation of CD8(+) cells and dramatically increased IL-2 and IFNgamma secretion. In addition, Letal induced the killing of cancer cells by CD8(+) and NK cells. These results suggest that Letal delivers activating signals to NK cells and promotes tumor immune surveillance by inducing the expansion of anti-tumor cytotoxic lymphocytes.