By using a β-actin–Raet1e transgenic (RaeTg)mouse in which an NKG2D ligand is constitutively expressed on all cells and tissues, we have demonstrated that when NKG2D is chronically exposed to this ligand in vivo, its expression at the cell surface is downmodulated, and the NKG2D-dependent NK cell functions, including tumor elimination, are impaired (11). This evidence concerns the gene KLRK1 and neoplasm.