Natural killer cell cytotoxicity and its regulation by inhibitory receptors

• Published in: Immunology Vol. 154; no. 3; pp. 383 - 393
• Main Author: Kumar, Santosh
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.07.2018; John Wiley and Sons Inc
• Subjects: activating receptor; Animals; Cell activation; Coding; Costimulatory and Inhibitory T-Cell Receptors - metabolism; cytotoxic synapse; Cytotoxicity; Cytotoxicity, Immunologic; Histocompatibility Antigens - immunology; Histocompatibility Antigens - metabolism; Humans; Immunological Synapses - immunology; Immunological Synapses - metabolism; Immunomodulation; immunoreceptor tyrosine‐based inhibitory motif (ITIM); inhibitory receptor; inhibitory synapse; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; killer‐cell Ig‐like receptor (KIR); Lymphocyte Activation - immunology; Lymphocyte receptors; Major histocompatibility complex; Molecular chains; natural killer cell; Natural killer cells; Receptors; Review; Signal Transduction; Signaling; T cell receptors; Target detection; Toxicity; activating receptor; inhibitory receptor; killer-cell Ig-like receptor (KIR); immunoreceptor tyrosine-based inhibitory motif (ITIM); natural killer cell; cytotoxic synapse; inhibitory synapse
• ISSN: 0019-2805; 1365-2567
• DOI: 10.1111/imm.12921

Summary Natural killer (NK) cells express an array of germ‐line encoded receptors that are capable of triggering cytotoxicity. NK cells tend to express many members of a given family of signalling molecules. The presence of many activating receptors and many members of a given family of signalling molecules can enable NK cells to detect different kinds of target cells, and to mount different kinds of responses. This contributes also to the robustness of NK cells responses; cytotoxic functions of NK cells often remain unaffected in the absence of selected signalling molecules. NK cells express many MHC‐I‐specific inhibitory receptors. Signals from MHC‐I‐specific inhibitory receptors tightly control NK cell cytotoxicity and, paradoxically, maintain NK cells in a state of proper responsiveness. This review provides a brief overview of the events that underlie NK cell activation, and how signals from inhibitory receptors intercept NK cell activation to prevent inappropriate triggering of cytotoxicity. “Natural killer (NK) cells utilize an array of germ‐line encoded activating and inhibitory receptors to sense their surroundings. The signals from activating receptors trigger, and those from inhibitory receptors prevent, NK cell cytotoxicity. This review provides a brief overview of the events that underlie NK cell cytotoxicity, and discusses how inhibitory receptors control NK cell cytotoxicity to prevent inappropriate responses.”