Cytolytic responses: cadherins put out the fire

Cytotoxic lymphocytes, such as natural killer (NK) cells and CD8(+) T cells, provide an essential defense against intracellular pathogens and tumors. During target cell recognition, these cells receive both activating and inhibitory signals. The cell must evaluate these opposing signals and determine the appropriate response: activation or inhibition. Classically, inhibitory signals are mediated by receptors that recognize MHC class I molecules (1). But recent studies, including one in this issue, suggest that MHC class I-independent inhibitory signals can also result in inhibition of cytotoxic cells.