A transmembrane-anchored rat RAE-1-like transcript as a ligand for NKR-P2, the rat ortholog of human and mouse NKG2D

NKG2D is a potent activating immunoreceptor that has been extensively characterized in NK cells and shown to lend costimulatory functions in CD8(+) T cells under certain conditions. The list is growing of ligands for NKG2D, which are distantly related to MHC class I molecule and are often up-regulated during cellular distress. Here, we describe the cloning of a novel (and incidentally the first) ligand for NKR-P2, the rat ortholog of human and mouse NKG2D, termed as rat RAE-1-like transcript (RRLT). The newly identified ligand is homologous to mouse RAE-1 family of proteins, but differs from them in being transmembrane anchored. The protein localizes to cell surface, and is expressed in a variety of tumor cell lines and tissues. Ectopic expression of the ligand induces NK cell activation, and renders the target cells susceptible to NK cell killing. In addition, the role of RRLT-NKR-P2 interaction in tumor killing has been demonstrated.