Natural killer cell signal integration balances synapse symmetry and migration.
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.
Culley
Fiona J
FJ
Division of Cell and Molecular Biology, Imperial College London, London, United Kingdom.
Johnson
Matthew
M
Evans
J Henry
JH
Kumar
Sunil
S
Crilly
Rupert
R
Casasbuenas
Juan
J
Schnyder
Tim
T
Mehrabi
Maryam
M
Deonarain
Mahendra P
MP
Ushakov
Dmitry S
DS
Braud
Veronique
V
Roth
Günter
G
Brock
Roland
R
Köhler
Karsten
K
Davis
Daniel M
DM
D000199:Actins / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D002469:Cell Separation; D002478:Cells, Cultured; D054992:Immunological Synapses / Q000276:immunology* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D014162:Transfection
D000199:Actins; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1