Nonstochastic coexpression of activation receptors on murine natural killer cells

Murine natural killer cells (NK) express lectin-like activation and inhibit ory receptors, including the CD94/NKG2 family of receptors that bind Qa-1, and the Ly-49 family that recognizes major histocompatibility complex class I molecules. Here, we demonstrate that crosslinking of NK cells with a new specific anti-Ly-49H mAb induced NK cell cytotoxicity and cytokine product ion. Ly-49H is expressed on a subset of NK cells and can be coexpressed wit h Ly-49 inhibitory receptors. However, unlike Ly-49 inhibitory receptors, L y-49H is not detectable on naive splenic CD3(+) T cells, indicating that Ly -49H may be an NK cell-specific activation receptor. In further contrast to the stochastically expressed Ly-49 inhibitory receptors, Ly-49H is prefere ntially expressed with the Ly-49D activation receptor, and expression of bo th Ly-49H and Ly-49D is augmented on NK cells that lack receptors for Qa-1 tetramers. On developing splenic NK1.1(+) cells, Ly-49D and Ly-49H are expr essed later than the inhibitory receptors. These results directly demonstra te that Ly-49H activates primary NK cells, and suggest that expression of L y-49 activation receptors by NK cells may be specifically regulated on NK c ell subsets. The simultaneous expression of multiple activation receptors b y individual NK cells contrasts with that of T cell antigen receptors and i s relevant to the role of NK cells in innate immunity.