CD56 at the human NK cell lytic immunological synapse

Abstract

CD56 is the main identifying cell surface molecule of NK cells and has been recently identified as a regulator of cytotoxic function in NK cell lines. Despite its newly defined role in lytic granule polarization and exocytosis, biological questions remain involving the localization and function of CD56 at the immunological synapse. Here we use confocal and structured illumination microscopy to demonstrate recruitment of CD56 to the peripheral supramolecular activating cluster (pSMAC) of the immunological synapse of lytic effector cells. We provide additional data demonstrating that cell lines that are less dependent on CD56 for function are not utilizing alternative pathways of cytotoxicity, and that those that are dependent on CD56 have normal expression of activating and adhesion receptors. Finally, we use actin reporter (LifeAct) expressing NK92 cell lines and live cell confocal microscopy to visualize live cell killing events with WT and CD56-KO cells. This work further characterizes the novel role for CD56 in cytotoxic function of NK cells and provides deeper insight into the role of CD56 at the NK cell immunological synapse.