Teaching Self Control

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Science  22 Apr 2011:
Vol. 332, Issue 6028, pp. 398
DOI: 10.1126/science.332.6028.398-b

Central to the design of an effective immune system is the ability to avoid disastrous consequences of autoimmune reactions in which healthy cells of a host organism are targeted for destruction rather than damaged cells or invading pathogens. In natural killer (NK) cells of the innate immune system, signaling through an array of activating and inhibitory receptors “educates” cells to respond appropriately to self ligands and ligands that signal cell damage or infection. Guia et al. report that in mice, potentially self-reactive NK cells are kept in check through sequestration of signalling molecules within the plasma membrane. Spot variable fluorescence correlation spectroscopy to monitor the movement of receptors revealed that, in NK cells genetically engineered to not be properly educated, inhibitory and activating receptors were confined together in domains where they were associated with an actin network below the membrane. When these cells were educated to allow appropriate activation, inhibitory receptors became diffusely distributed, whereas activating receptors were present in nanodomains or “rafts” characteristic of active receptor signaling. This mechanism, as compared to transcriptional reprogramming, may allow the NK cells greater flexibility to switch between an unresponsive state and a state in which they are competent to respond to stimuli.

Sci. Signal. 4, ra21 (2011).

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