ASSOCIATION OF DAP12 WITH ACTIVATING CD94 NKG2C NK CELL RECEPTORS/

While the inhibitory NK cell receptors for MHC class I express immunor eceptor tyrosine-based inhibitory motifs that recruit intracellular ty rosine phosphatases and prevent NK cell effector function, the activat ing NK cell receptors lack intrinsic sequences required for cellular s timulation. CD94/NKG2C, an activating NK cell receptor of the C-type l ectin superfamily that binds to HLA-E, noncovalently associates with D AP12, a membrane receptor containing an immunoreceptor tyrosine-based activating motif. Efficient expression of CD94/NKG2C on the cell surfa ce requires the presence of DAP12, and charged residues in the transme mbrane domains of DAP12 and NKG2C are necessary for this interaction. These results provide a molecular basis for the assembly of NK cell re ceptors for MHC class I involved in cellular activation and inhibition .