Ambrose, Ashley RAshley RAmbroseHazime, Khodor SKhodor SHazimeWorboys, Jonathan DJonathan DWorboysNiembro-Vivanco, OlatzOlatzNiembro-VivancoDavis, Daniel MDaniel MDavis2025-01-312025-01-312020-09-22PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2020, 117 (38), pp.23717-237200027-8424https://hdl.handle.net/10044/1/117052<jats:title>Significance</jats:title> <jats:p>Cytotoxic immune cells kill cancer and virally infected cells through secretion of perforin and granzymes at immune synapses. It has recently been shown that cytotoxic T cells secrete membraneless protein structures, termed SMAPs, comprising perforin and granzyme within a shell of the glycoprotein TSP-1. Here, using a novel imaging technique termed "shadow imaging," we quantitatively assessed synaptic secretion from individual human NK cells. Upon ligation of activating receptors, NK cells secreted vesicles as well as membraneless SMAPs containing TSP-1, perforin, and granzyme B. Super-resolution microscopy revealed that NK cell SMAPs were larger than those secreted by T cells. Heterogeneity in NK cell synaptic secretion is likely important for the different effector functions of NK cell subtypes.</jats:p>Science & TechnologyMultidisciplinary SciencesScience & Technology - Other Topicsnatural killer cellsimmune synapsesupramolecular attack particlesSERGLYCINSynaptic secretion from human natural killer cells is diverse and includes supramolecular attack particlesJournal Article10.1073/pnas.2010274117https://doi.org/10.1073/pnas.20102741171091-6490