Natural killer cells: Integrating diversity with function

Department of Hepatology, Division of Medicine, Imperial College, London, UK.
Immunology (Impact Factor: 3.8). 05/2009; 126(4):449-57. DOI: 10.1111/j.1365-2567.2009.03045.x
Source: PubMed


The key role of natural killer cells in many aspects of the immune response is now being recognized. The last decade has seen an exponential increase in our understanding of the workings of these cells. Receptor diversity is crucial in allowing natural killer cells to respond effectively to a variety of different pathogens. This article reviews aspects of natural killer cell diversity that combine to generate populations of functional natural killer cells that exist within both the individual and throughout the population at large.

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Available from: Kuldeep Cheent, Jan 21, 2014
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    • "There are two main groups of KIR haplotypes: group A including three genes encoding for inhibitory KIRs (2DL1, 2DL2 and 3DL1) and one activating KIR (2DS4), and group B including seven genes (2DS1, 2DS2, 2DS3, 2DL2, 2DL5, 3DS1 and 2DS5) and mostly encoding for activating receptors (Rea et al., 2013). In general, NK cells are richer with activating receptors than with inhibitory receptors (Cheent and Khakoo, 2008). NK cells mediated cytotoxicity and T-cell receptor (TCR) mediated killing are inhibited due to the ligation action between KIR and HLA class I molecules on target cells and this inhibition effect of KIRs is controlled by immunoreceptor tyrosine based inhibition motifs (ITIM) (Dukers et al., 2001). "
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    ABSTRACT: In addition to their important role in fighting infection, natural killer cells are cytotoxic to cancer cells. Studies demonstrated that some KIR genes were responsible for the reduction of the risk of Hodgkin's lymphoma (HL) while others were associated with an increased risk of HL. The aim of this study is to assess KIR genotypic distribution in Lebanese patients with Hodgkin's lymphoma. KIR genotype was analyzed in 41 HL patients and 120 healthy Lebanese individuals using the KIR Genotyping SSP kit. No significant association between HL and any KIR gene was found. Among HL patients, the AA, AB, and BB genotype frequencies were, respectively, 41.46%, 43.9% and 14.63% with an A:B ratio of 1.73:1. As for the controls, the AA, AB, and BB genotype frequencies were, respectively, 39.17%, 50%, and 10.83% with an A:B ratio of 1.79:1. In this first study from the Mediterranean region, KIR genotype does not seem to be associated with Hodgkin's lymphoma. Further clinical and translational research is needed to rule out the protective or predisposing role of KIR genes in this important clinical entity.
    Meta Gene 06/2015; 4. DOI:10.1016/j.mgene.2015.02.004
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    • "NK cells are especially important in combating viral infections in general and HCMV in particular, and consequently, NK-deficient patients succumb to lethal HCMV infections (Orange, 2013). NK cell activity is governed by integrating signals from a panel of activating and inhibitory receptors (Cheent and Khakoo, 2009). One of the key activating NK receptors is NKG2D, a C-type lectin that recognizes a family of major histocompatibility complex (MHC)-like stress-induced ligands: MHC class I polypeptide-related sequences (MIC) A and B, and UL16 binding proteins (ULBP) 1–6 (Ferná ndez-Messina et al., 2012). "
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    Cell Reports 02/2015; 10(6). DOI:10.1016/j.celrep.2015.01.029 · 8.36 Impact Factor
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    • "The reason for the lack of concordance between FccRIIIA binding and ADCC activity is unknown and should be investigated. The granzyme B and perforin pathway is important to NK cell-mediated cytotoxicity [16]. KHYG-1 cells reportedly express granzyme M at high levels constitutively, but they express granzyme B and perforin only at low levels in the absence of stimulation [19]. "
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    ABSTRACT: The Fc region of human IgG1 mediates effector function via binding to Fc receptors and complement activation. The H and L chains of IgG1 antibodies are joined by four interchain disulfide bonds. In this study, these bonds within the therapeutic IgG1 rituximab (RTX) were cleaved either by mild reduction followed by alkylation or by mild S-sulfonation; consequently, two modified RTXs - A-RTX (alkylated) and S-RTX (S-sulfonated) - were formed, and both were almost as potent as unmodified RTX when binding CD20 antigen. Unexpectedly, each modified RTX had a higher binding affinity for FcRIIIA (CD16A) than did unmodified RTX. However, S-RTX and A-RTX were each less potent than RTX in an assay of antibody-dependent cellular cytotoxicity (ADCC). In this ADCC assay, each modified RTX showed decreased secretion of granzyme B, but no change in perforin secretion, from effector cells. These results provide significant information on the structures within IgG1 that are involved in binding FcγRIIIA, and they may be useful in the development of therapeutic antagonists for FcγRIIIA.
    Biochemical and Biophysical Research Communications 06/2013; 436(3). DOI:10.1016/j.bbrc.2013.05.137 · 2.30 Impact Factor
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