Jul 29, 2009

Natural killer cell signal integration balances synapse symmetry and migration

PLoS Biology
Fiona J CulleyDaniel M Davis

Abstract

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 inhib...Continue Reading

Mentioned in this Paper

Pathologic Cytolysis
Neuro-Oncological Ventral Antigen 2
Flow Cytometry
ITGB2 wt Allele
Biochemical Pathway
Conjugation
T-Lymphocyte
Lamellipodia
Transfection
Antigen-Presenting Cells

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