Research ArticleImmunology

Educated natural killer cells show dynamic movement of the activating receptor NKp46 and confinement of the inhibitory receptor Ly49A

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Sci. Signal.  13 Feb 2018:
Vol. 11, Issue 517, eaai9200
DOI: 10.1126/scisignal.aai9200

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Receptor dynamics shape NK cell function

Natural killer (NK) cells are a subset of innate lymphoid cells that target virally infected and malignant cells. An education process ensures that activating receptors promote NK cell activation in response to infected or abnormal cells and that inhibitory receptors prevent inappropriate NK cell activation by healthy cells. Cells that lack inhibitory receptors are hyporesponsive. Staaf et al. found that the activating receptor NKp46 and the inhibitory receptor Ly49A exhibited dynamic movements in the plasma membrane that differed between educated and hyporesponsive NK cells. Although both receptors were generally restricted to membrane microdomains, NKp46 molecules spent less time in an individual microdomain and diffused faster on educated cells compared to hyporesponsive cells. Conversely, Ly49A molecules were overall more constrained and diffused more slowly on educated cells. Interfering with receptor dynamics reduced signaling by NKp46, indicating that the dynamic movements of these receptors are likely important determinants of NK cell responsiveness.