Lipid order and charge protect killer T cells from accidental death
Open Access
- 27 November 2019
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 10 (1), 1-13
- https://doi.org/10.1038/s41467-019-13385-x
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, exposed phosphatidylserine sequesters and inactivates perforin. The resulting resistance of CTLs to perforin explains their ability to kill target cells in rapid succession and to survive these encounters. Furthermore, these mechanisms imply an unsuspected role for plasma membrane organization in protecting cells from immune attack.Keywords
Funding Information
- RCUK | Biotechnology and Biological Sciences Research Council (BB/J005932/1, BB/J006254/1, BB/N015487/1)
- RCUK | Engineering and Physical Sciences Research Council (EP/M028100/1)
- Dr. Mortimer and Theresa Sackler Foundation
- Department of Health | National Health and Medical Research Council (1059126)
- Australian Cancer Research Foundation
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