Journal article

Rapid and Unidirectional Perforin Pore Delivery at the Cytotoxic Immune Synapse

Jamie A Lopez, Misty R Jenkins, Jesse A Rudd-Schmidt, Amelia J Brennan, Jillian C Danne, Stuart I Mannering, Joseph A Trapani, Ilia Voskoboinik



The effective engagement of cytotoxic lymphocytes (CLs) with their target cells is essential for the removal of virus-infected and malignant cells from the body. The spatiotemporal properties that define CL engagement and killing of target cells remain largely uncharacterized due to a lack of biological reporters. We have used a novel live cell microscopy technique to visualize the engagement of primary human and mouse CL with their targets and the subsequent delivery of the lethal hit. Extensive quantitative real-time analysis of individual effector-target cell conjugates demonstrated that a single effector calcium flux event was sufficient for the degranulation of human CLs, resulting in t..

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Awarded by Juvenile Diabetes Research Foundation

Funding Acknowledgements

J.A.L. is supported by a National Health and Medical Research Council Postdoctoral Training Fellowship and M.R.J. by a National Health and Medical Research Council/RG Menzies Postdoctoral Training Fellowship. This work was supported by Juvenile Diabetes Research Foundation Grant JDRF 17-2011-527 (to S. I. M.). I. V. and J.A.T. are supported by fellowships, project, and program grants from the National Health and Medical Research Council.