(A) Receptor-ligand interactions modulating NK cell function. MHC class I interacts with the inhibitory receptor LIR-1, and HLA-E interacts with the CD94/NKG2A receptor; both interactions result in inhibition of NK cell function. The ligands MICA, ULBP1/2, and MICB all interact with the NKG2D receptor, resulting in NK cell activation. (B) HCMV genes encode proteins that modify NK cell responses. NK cell evasion can be mediated by the HCMV UL18 gene product (gpUL18), a ligand for the inhibitory receptor LIR-1; the UL16 gene product (gpUL16), which downregulates the NKG2D activating ligands MICB and ULBP1/2; the UL142 gene product (gpUL142), which downregulates the NKG2D ligand MICA; an epitope from the leader peptide segment of the UL40-encoded protein, which loads HLA-E, driving an inhibitory signal to the NK cell via the CD94/NKG2A receptor; and a miRNA from the UL112 gene, which interacts with a cellular miRNA to inhibit MICB expression by preventing translation of MICB mRNA.