Immune Netw.  2012 Dec;12(6):240-246. 10.4110/in.2012.12.6.240.

Signaling for Synergistic Activation of Natural Killer Cells

• Kwon HJ
• Kim HS

• KMID: 2150755
• DOI: http://doi.org/10.4110/in.2012.12.6.240

Abstract

Natural killer (NK) cells play a pivotal role in early surveillance against virus infection and cellular transformation, and are also implicated in the control of inflammatory response through their effector functions of direct lysis of target cells and cytokine secretion. NK cell activation toward target cell is determined by the net balance of signals transmitted from diverse activating and inhibitory receptors. A distinct feature of NK cell activation is that stimulation of resting NK cells with single activating receptor on its own cannot mount natural cytotoxicity. Instead, specific pairs of co-activation receptors are required to unleash NK cell activation via synergy-dependent mechanism. Because each co-activation receptor uses distinct signaling modules, NK cell synergy relies on the integration of such disparate signals. This explains why the study of the mechanism underlying NK cell synergy is important and necessary. Recent studies revealed that NK cell synergy depends on the integration of complementary signals converged at a critical checkpoint element but not on simple amplification of the individual signaling to overcome intrinsic activation threshold. This review focuses on the signaling events during NK cells activation and recent advances in the study of NK cell synergy.

Keyword

Natural killer cell; Activating receptor; Signaling; Synergy

MeSH Terms

Killer Cells, Natural
Viruses

Figure

• 

  Figure 1 Proposed model for synergistic activation of NK cells. Complemetary phosphorylation of SLP-76 by synergizing receptors, NKG2D and 2B4, is required for optimal activation of Vav1 and thereby to overcome inhibition by c-Cbl.

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