Article

Structural insights into activation of antiviral NK cell responses

Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Immunological Reviews (Impact Factor: 12.91). 11/2012; 250(1):239-57. DOI: 10.1111/j.1600-065X.2012.01168.x
Source: PubMed

ABSTRACT Natural killer (NK) cells are key components of innate immune responses, providing surveillance against cells undergoing tumorigenesis or infection, by viruses or internal pathogens. NK cells can directly eliminate compromised cells and regulate downstream responses of the innate and acquired immune systems through the release of immune modulators (cytokines, interferons). The importance of the role NK cells play in immune defense was demonstrated originally in herpes viral infections, usually mild or localized, which become severe and life threatening in NK-deficient patients . NK cell effector functions are governed by balancing opposing signals from a diverse array of activating and inhibitory receptors. Many NK receptors occur in paired activating and inhibitory isoforms and recognize major histocompatibility complex (MHC) class I proteins with varying degrees of peptide specificity. Structural studies have made considerable inroads into understanding the molecular mechanisms employed to broadly recognize multiple MHC ligands or specific pathogen-associated antigens and the strategies employed by viruses to thwart these defenses. Although many details of NK development, signaling, and integration remain mysterious, it is clear that NK receptors are key components of a system exquisitely tuned to sense any dysregulation in MHC class I expression, or the expression of certain viral antigens, resulting in the elimination of affected cells.

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    • "Virus-infected cells often induce or increase the expression of ligands at their surface, allowing for recognition by NK cell activating receptors, including NKG2D, DNAM-1, CD94-NKG2C; the NCR receptors NKp46, NKp30, NKp44; and others (19, 20, 22). The ligands include host stress-induced molecules and viral proteins (20). "
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    Frontiers in Immunology 05/2014; 5:192. DOI:10.3389/fimmu.2014.00192
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    • "NKp44 and NKp46 bind influenza and other viral hemagglutinins (HAs) mainly through recognition by the HA of terminal sialic acid moieties (the cellular receptor for HAs) on N-linked glycans of these NCRs (72, 76, 77). Although this mechanism would allow NKp44 and NKp46 to bind a wide variety of viruses, due to the ability of HAs to bind sialic acid-containing glycoproteins in general, this is probably not the full story, since recognition would not depend on the NCR ectodomain itself, but only on the fact that NKp44 and NKp46 are glycoproteins with terminal sialic acids (13). Binding of NKp46 to heparan sulfate proteoglycans has also been described (78), but the biological relevance of this interaction is unclear. "
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    Immunological Reviews 11/2012; 250(1):5-9. DOI:10.1111/imr.12007 · 12.91 Impact Factor
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