Abstract
Natural Killer (NK) cells are innate immune lymphocytes specializing in recognition and killing of tumors and pathogens, using an array of activating and inhibitory receptors. NK inhibition is mediated by a large repertoire of inhibitory receptors, whereas a limited number of activating NK cell receptors execute NK cell activation. The ligands recognized by the activating receptors are stress-induced, pathogen derived, tumor specific and even self ligands. However, the full spectrum of NK cell receptors and ligands that control NK cell activity remains uncharacterized. Here we demonstrate that Paired Ig-Like type 2 Receptor Alpha (PILRα), binds a distinct human NK cell sub-population present in the peripheral blood and also in the decidua. We further demonstrate that the interaction of NK cells with PILRα expressing targets lead to elevated IFNγ secretion and cytotoxicity. In conclusion, we present here a novel NK activating ligand which binds and activates an unknown NK receptor expressed on a unique NK cell subset.
Highlights
Natural Killer (NK) cells express a vast combinatorial array of receptors that can activate or inhibit NK-mediated cytotoxicity and cytokine secretion, in response to oncogenic transformation, bacterial, fungal and viral infections [1][2]
We have previously shown that the viral HA protein binds NKp44 and NKp46, leading to an increase in NK cell mediated killing of influenzainfected cells [14][15]
PILRα was shown to bind O-linked glycosylated receptors, such as Collectin12, PILR-associating neural protein (PANP) and NPDC [17] [18], we sought to investigate whether PILRα might interact with NKp46 and NKp44
Summary
NK cells express a vast combinatorial array of receptors that can activate or inhibit NK-mediated cytotoxicity and cytokine secretion, in response to oncogenic transformation, bacterial, fungal and viral infections [1][2]. When encountered with target cells, the decision to kill or spare the target cells is determined by a balance of signals delivered by these receptors, which recognize a variety of ligands on the target cells [3][4]. NK cell cytotoxicity is positively controlled by activating receptors. The most prominent family of NK cell activating receptors is the Natural Cytotoxicity Receptors (NCR), which includes: NKp30 [5], NKp44 [6], and NKp46 [7]. The NCRs recognize a variety of tumor and pathogen-derived molecules. NKp30 recognizes B7H6 which is expressed on tumor cells [9] and the pp protein of human cytomegalovirus [10]. The full repertoire of NCR ligands, including self and tumor ligands, remains to be established
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