NK cells preferentially recognize and kill cells that lack expression of MHC class I 1. While inhibitory receptors expressing immunoreceptor tyrosine-based inhibition motifs prevent NK cells from harming tissues expressing normal levels of classical or nonclassical MHC class I (for a review, see reference 2), what turns on NK cells? Recent reports 3,4, including Smith et al. in this issue 4, are beginning to unfold the receptors and signaling pathways involved in positive activation of NK cells.
Unlike T cells or B cells, which recognize antigen using clonally restricted receptors generated by gene rearrangement, NK cells appear to use a variety of different, nonrearranging receptors to initiate cytolytic activity and cytokine production (for a review, see reference 5). Many of these activating receptors are not restricted to NK cells; most are also...
