Journal article
Lipid order and charge protect killer T cells from accidental death
JA Rudd-Schmidt, AW Hodel, T Noori, JA Lopez, HJ Cho, S Verschoor, A Ciccone, JA Trapani, BW Hoogenboom, I Voskoboinik
Nature Communications | NATURE PUBLISHING GROUP | Published : 2019
Abstract
Killer T cells (cytotoxic T lymphocytes, CTLs) maintain immune homoeostasis by eliminating virus-infected and cancerous cells. CTLs achieve this by forming an immunological synapse with their targets and secreting a pore-forming protein (perforin) and pro-apoptotic serine proteases (granzymes) into the synaptic cleft. Although the CTL and the target cell are both exposed to perforin within the synapse, only the target cell membrane is disrupted, while the CTL is invariably spared. How CTLs escape unscathed remains a mystery. Here, we report that CTLs achieve this via two protective properties of their plasma membrane within the synapse: high lipid order repels perforin and, in addition, expo..
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Grants
Awarded by Dr. Mortimer and Theresa Sackler Foundation
Funding Acknowledgements
We thank Richard Thorogate and Shu Chen for technical support; Natalya Lukoyanova for advice on electron microscopy experiments; Helen Saibil, Ricardo Henriques and Dylan Owen for discussions and comments on the manuscript. We also thank the following Peter MacCallum Cancer Centre core facilities for technical support: Ralph Rossi and the Flow Cytometry facility, Sarah Ellis and the Centre for Advanced Histology and Microscopy. This work has been funded by the NHMRC Project Grant (1128587), the NHMRC Fellowship (1059126), the BBSRC (BB/J005932/1, BB/J006254/1 and BB/N015487/1); the EPSRC (EP/M028100/1); and the Sackler Foundation. This research was supported by the Australian Cancer Research Foundation (for the Peter MacCallum Cancer Centre core facilities).