Physical and functional independency of p70 and p58 natural killer (NK) cell receptors for HLA class I: their role in the definition of different groups of alloreactive NK cell clones.

Vitale, Massimo; Sivori, Simona; Pende, Daniela; Augugliaro, Raffaella; Donato, C Di; Amoroso, Antonio; Malnati, Mauro S.; Bottino, Cristina; Moretta, Lorenzo; Moretta, Alessandro

doi:10.1073/pnas.93.4.1453

Cited by 102 publications

(69 citation statements)

References 33 publications

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“…16 Among the numerous KIR genes, the KIR3DL1/3DS1 locus is of particular interest with respect to AS because KIR3DL1 is the only KIR that recognizes HLA-B molecules of the Bw4 serotype, including HLA-B27. 36 KIR3DL1 is an inhibitory receptor that interacts with HLA-Bw4 to suppress the cytolytic capacity of NK or T cells [36][37][38] and likely plays a role in protecting against autoimmunity. 15,23 A counterpart of KIR3DL1 is the activating receptor, KIR3DS1.…”

Section: Introductionmentioning

confidence: 99%

Contribution of functional KIR3DL1 to ankylosing spondylitis

et al. 2010

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Increasing evidence points to a role for killer immunoglobulin-like receptors (KIRs) in the development of autoimmune diseases. In particular, a positive association of KIR3DS1 (activating receptor) and a negative association of KIR3DL1 (inhibitory receptor) alleles with ankylosing spondylitis (AS) have been reported by several groups. However, none of the studies analyzed these associations in the context of functionality of polymorphic KIR3DL1. To better understand how the KIR3DL1/3DS1 genes determine susceptibility to AS, we analyzed the frequencies of alleles and genotypes encoding functional (KIR3DL1*F) and non-functional (KIR3DL1*004) receptors. We genotyped 83 AS patients and 107 human leukocyte antigen (HLA)-B27-positive healthy controls from the Russian Caucasian population using a two-stage sequence-specific primer PCR, which distinguishes KIR3DS1, KIR3DL1*F and KIR3DL1*004 alleles. For the patients carrying two functional KIR3DL1 alleles, those alleles were additionally genotyped to identify KIR3DL1*005 and KIR3DL1*007 alleles, which are functional but are expressed at low levels. KIR3DL1 was negatively associated with AS at the expense of KIR3DL1*F but not of KIR3DL1*004. This finding indicates that the inhibitory KIR3DL1 receptor protects against the development of AS and is not simply a passive counterpart of the segregating KIR3DS1 allele encoding the activating receptor. However, analysis of genotype frequencies indicates that the presence of KIR3DS1 is a more important factor for AS susceptibility than the absence of KIR3DL1*F. The activation of either natural killer (NK) or T cells via the KIR3DS1 receptor can be one of the critical events in AS development, while the presence of the functional KIR3DL1 receptor has a protective effect. Nevertheless, even individuals with a genotype that carried two inhibitory KIR3DL1 alleles expressed at high levels could develop AS.

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Section: Introductionmentioning

confidence: 99%

Contribution of functional KIR3DL1 to ankylosing spondylitis

et al. 2010

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“…Since some structural families contain both activating and inhibitory receptors, trying to understand how NK cell activity is regulated is often complicated. 25 At steady state, the inhibitory receptors (KIRs and CD94/NKG2A/B), which bind to various MHC-I molecules present on almost all cell types, inhibit NK cell activation and prevent NK cell-mediated killing. Under stress conditions, cells downregulate MHC-I expression, causing NK cells to lose inhibitory signaling and be activated in a process called 'missing-self recognition'.…”

Section: Conception Of Nk Cellsmentioning

confidence: 99%

NK cell-based immunotherapy for malignant diseases

et al. 2013

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Natural killer (NK) cells play critical roles in host immunity against cancer. In response, cancers develop mechanisms to escape NK cell attack or induce defective NK cells. Current NK cell-based cancer immunotherapy aims to overcome NK cell paralysis using several approaches. One approach uses expanded allogeneic NK cells, which are not inhibited by self histocompatibility antigens like autologous NK cells, for adoptive cellular immunotherapy. Another adoptive transfer approach uses stable allogeneic NK cell lines, which is more practical for quality control and large-scale production. A third approach is genetic modification of fresh NK cells or NK cell lines to highly express cytokines, Fc receptors and/or chimeric tumor-antigen receptors. Therapeutic NK cells can be derived from various sources, including peripheral or cord blood cells, stem cells or even induced pluripotent stem cells (iPSCs), and a variety of stimulators can be used for large-scale production in laboratories or good manufacturing practice (GMP) facilities, including soluble growth factors, immobilized molecules or antibodies, and other cellular activators. A list of NK cell therapies to treat several types of cancer in clinical trials is reviewed here. Several different approaches to NK-based immunotherapy, such as tissue-specific NK cells, killer receptor-oriented NK cells and chemically treated NK cells, are discussed. A few new techniques or strategies to monitor NK cell therapy by non-invasive imaging, predetermine the efficiency of NK cell therapy by in vivo experiments and evaluate NK cell therapy approaches in clinical trials are also introduced.

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“…Thus, as mentioned, the EB6b mAb recognizes both KIR2DL1 (inhibitory) and KIR2DS1 (activating) molecules, whereas the GL183 mAb recognizes both KIR2DL2/3 (inhibitory) and KIR2DS2 (activating) molecules. Moreover, the KIR3DL1-specific Z27 mAb 47 also reacts with an activating KIR (likely represented by KIR3DS1). 48 In the latter case, however, the fluorescence intensity is different in NK cells expressing one or another KIR3D receptor.…”

Section: Characterization Of Nk Cell Lines From Ldgl Patientsmentioning

confidence: 99%