Natural killer (NK) cell activity is governed by the opposing actions of activating and inhibitory receptors at the immunological synapse. In Science Signaling, Pageon et al. use super-resolution fluorescence microscopy to observe changes in the nanoscale organization of the inhibitory receptor KIR2DL1 after receptor ligation. Resting NK cells have discrete nanoclusters of KIR2DL1 that after ligation become denser aggregates. Surprisingly, ligation of the activating receptor NKG2D also triggers tighter clustering of KIR2DL1 but not of other surface molecules such as HLA, which indicates crosstalk between the two NK receptors. Unlike ligation of KIR2DL1, NKG2D-induced receptor clustering requires remodeling of the actin cytoskeleton. KIR2DL1 remodeling could lower the threshold required for transmission of its inhibitory signals via the phosphatase SHP-1. Whether this remodeling increases the proximity between KIR2DL1 and NKG2D or other downstream signaling molecules remains unknown.
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Dempsey, L. Clustering NK receptors. Nat Immunol 14, 892 (2013). https://doi.org/10.1038/ni.2701
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DOI: https://doi.org/10.1038/ni.2701
