Research ArticleImmunology

Superresolution Microscopy Reveals Nanometer-Scale Reorganization of Inhibitory Natural Killer Cell Receptors upon Activation of NKG2D

Sci. Signal.  23 Jul 2013:
Vol. 6, Issue 285, pp. ra62
DOI: 10.1126/scisignal.2003947

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Imaging Receptor Crosstalk

Natural killer (NK) cells mediate the immune response to virally infected cells and tumor cells, and their activation state depends on the integration of signals from multiple activating and inhibitory cell-surface receptors. The limitations of light microscopy have prevented a clear understanding of the distribution of these receptors, so Pageon et al. used superresolution fluorescence microscopy to view the organization of the inhibitory receptor KIR2DL1 on the surface of human NK cells. KIR2DL1 was constitutively organized in nanometer-scale clusters that became smaller and denser when cells were treated with a KIR2DL1-specific antibody; unexpectedly however, a similar redistribution of KIR2DL1 occurred in response to engagement of the activating receptor NKG2D. Together, these data reveal crosstalk between activating and inhibitory receptors that may have important effects on NK cell function.