In lymphopenic C57Bl/6 mice, CMV-specific NK cell activation is mediated via the NK cell-expressed activating receptor Ly49H, the ligand of which is the murine CMV (mCMV)-encoded protein m157 (57–59), similar to NKG2C+ NK cells that expand upon HCMV infection or reactivation in humans. This evidence concerns the gene KLRC2 and cytomegalovirus infection.