Stress Signals Activate Natural Killer Cells

The mechanisms that regulate NK cell function as a first line of defense against infection and transformation have exceeded our expectations in terms of their sophistication and complexity. Quiescent, circulating NK cells can be activated by either soluble mediators, such as interferons and cytokines, or by direct cell–cell contact. Activation occurs during contact not only when NK cells sense the loss of MHC class I expression on the surface of other cells but also with cells that have undergone other alterations induced by infection or cellular stress. Notably, expression of ligands for receptor NKG2D induced by stress or transformation results in activation signals that can overcome the inhibition mediated by MHC class I–specific receptors (1–4). Yet another mode of NK cell activation upon cellular stress is described in this issue by Michaëlsson et al. (5). Replacement of a peptide...