Cell biological steps and checkpoints in accessing NK cell cytotoxicity

Natural killer (NK) cell‐mediated cytotoxicity is governed by the formation of a lytic immune synapse in discrete regulated steps, which give rise to an extensive array of cellular checkpoints in accessing NK cell‐mediated cytolytic defense. Appropriate progression through these cell biological steps is critical for the directed secretion of specialized secretory lysosomes and subsequent target cell death. Here we highlight recent discoveries in the formation of the NK cell cytolytic synapse as well as the molecular steps and cell biological checkpoints required for this essential host defense process. The March 2014 issue contains a Special Feature on NK cell recognition of unconventional ligands. Natural Killer (NK) cells are bone marrow derived lymphocytes capable of mediating rapid effector responses following pathogen detection in mammals. The name “Natural Killer” derives from the ability of these cells to spontaneously lyse a large range of leukemia cell lines in vitro without prior sensitization. The reviews included in this Special Feature of Immunology and Cell Biology highlight the multifaceted roles of NK cells in detecting unconventional ligands and countering a large range of pathogens and malignancies. Covering a range of topics, including the way adhesion molecules and activating receptors are central to NK cell recognition of their targets, the reviews also highlight some of the challenges that lie ahead in harnessing NK cell function and advancing NK cell immunotherapy strategies to persistent infection, cancer and bone marrow transplantation. Immunology and Cell Biology thanks the coordinator of this Special Feature – Nicholas Huntington – for his planning and input. Further background information on this important topic is available through the accompanying web focus which links to related articles from across Nature Publishing Group.