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Critical Reviews™ in Immunology
IF: 1.352 5-Year IF: 3.347 SJR: 1.022 SNIP: 0.55 CiteScore™: 2.19

ISSN Print: 1040-8401
ISSN Online: 2162-6472

Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.2014012220
pages 455-465

Inhibitory Receptor-Mediated Regulation of Natural Killer Cells

Elisenda Alari-Pahissa
Ludwig Center for Cancer Research, Department of Oncology, University of Lausanne, Epalinges, Switzerland
Camille Grandclement
Ludwig Center for Cancer Research, Department of Oncology, University of Lausanne, Epalinges, Switzerland
Beena Jeevan-Raj
Ludwig Center for Cancer Research, Department of Oncology, University of Lausanne, Epalinges, Switzerland
Werner Held
Ludwig Center for Cancer Research, Department of Oncology, University of Lausanne, Epalinges, Switzerland

ABSTRACT

Natural killer (NK) cells are capable of directly recognizing pathogens, pathogen-infected cells, and transformed cells. NK cells recognize target cells using approximately 100 germ-line encoded receptors, which display activating or inhibitory function. NK cell activation usually requires the engagement of more than one receptor, and these may contribute distinct signaling inputs that are required for the firm adhesion of NK cells to target cells, polarization, and the release of cytotoxic granules, as well as the production of cytokines. In this article we discuss receptor-mediated mechanisms that counteract NK cell activation. The distinct intracellular inhibitory signaling pathways and how they can dominantly interfere with NK cell activation signaling events are discussed first. In addition, mechanisms by which inhibitory receptors modulate cellular activation at the level of receptor−ligand interactions are described. Receptor-mediated inhibition of NK cell function serves three main purposes: ensuring tolerance of NK cells to normal cells, enabling NK cell responses to aberrant host cells that have lost an inhibitory ligand, and, finally, allowing the recognition of certain pathogens that do not express inhibitory ligands.