Natural killer cell signal integration balances synapse symmetry and migration.
- Others:
- Division of Cell and Molecular Biology [London] ; Imperial College London
- Department of Respiratory Medicine ; Imperial College London
- National Heart and Lung Institute ; Imperial College London
- Institut de pharmacologie moléculaire et cellulaire (IPMC) ; Université Nice Sophia Antipolis (1965 - 2019) (UNS) ; COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)
- Department of Molecular Biology ; Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen
- Department of Biochemistry ; Radboud University [Nijmegen]
- Department of Microsystems Engineering [Freiburg] (IMTEK) ; University of Freiburg [Freiburg]
- University of Nijmegen, the Netherlands
Citation
Description
Natural killer (NK) cells discern the health of other cells by recognising the balance of activating and inhibitory ligands expressed by each target cell. However, how the integration of activating and inhibitory signals relates to formation of the NK cell immune synapse remains a central question in our understanding of NK cell recognition. Here we report that ligation of LFA-1 on NK cells induced asymmetrical cell spreading and migration. In contrast, ligation of the activating receptor NKG2D induced symmetrical spreading of ruffled lamellipodia encompassing a dynamic ring of f-actin, concurrent with polarization towards a target cell and a "stop" signal. Ligation of both LFA-1 and NKG2D together resulted in symmetrical spreading but co-ligation of inhibitory receptors reverted NK cells to an asymmetrical migratory configuration leading to inhibitory synapses being smaller and more rapidly disassembled. Using micropatterned activating and inhibitory ligands, signals were found to be continuously and locally integrated during spreading. Together, these data demonstrate that NK cells spread to form large, stable, symmetrical synapses if activating signals dominate, whereas asymmetrical migratory "kinapses" are favoured if inhibitory signals dominate. This clarifies how the integration of activating and inhibitory receptor signals is translated to an appropriate NK cell response.
Abstract
International audience
Additional details
- URL
- https://hal.archives-ouvertes.fr/hal-00416571
- URN
- urn:oai:HAL:hal-00416571v1
- Origin repository
- UNICA