ULBPs, novel MHC class I-related molecules bind to CMV glycoprotein UL16 and stimulate NK cytotoxicity through the NKG2D receptor

The human cytomegalovirus glycoprotein, UL16, binds to two members of a novel family of molecules, the ULBPs, and to the MHC class I homolog, MICE. The ULBPs are GPI-linked glycoproteins belonging to the extended MHC class I family but are only distantly related to MICE. The ULBP and MICE molecules are ligands for the activating receptor, NKG2D/DAP10, and this interaction is blocked by a soluble form of UL16. The ULBPs stimulate cytokine and chemokine production from NK cells, and expression of ULBPs in NK cell-resistant target cells confers susceptibility to NK cell cytotoxicity. Masking of NK cell recognition of ULBP or MIC antigens by UL16 provides a potential mechanism by which human cytomegalovirus-infected cells might evade attack by the immune system.