FcγRIIIa-158V/F polymorphism influences the binding of IgG by NK cell FcγRIIIa, independent of the FcγRIIIa-48L/R/H phenotype

Koene, Harry R.; Kleijer, Marion; Algra, Johan; Roos, Dirk; Bome, Albert E.G.Kr. von dem; Haas, Masja de

doi:10.1016/s0165-2478(97)85823-3

Cited by 209 publications

(280 citation statements)

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“…In humans, macrophages express all three Fcg receptors, whereas neutrophils and NK cells express predominantly FcgRII and FcgRIII (Koene et al, 1997). Sequence nucleotide polymorphisms within the FCGR2 and FCGR3 loci in humans alter their binding affinities to IgG1 Mabs, and ultimately impact on downstream effector cell engagement of therapeutic Mabs such as the anti-CD20 antibody Rituximab (Weng and Levy, 2003).…”

Section: Resultsmentioning

confidence: 99%

Macrophages and Fc-receptor interactions contribute to the antitumour activities of the anti-CD40 antibody SGN-40

et al. 2008

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Section: Resultsmentioning

confidence: 99%

Macrophages and Fc-receptor interactions contribute to the antitumour activities of the anti-CD40 antibody SGN-40

et al. 2008

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“…Elimination of an ineffective mAb from the mixture and/or higher dosing could improve efficacy. Alternatively, because ADCC is an important mechanism of action for these mAbs (23), polymorphisms of the ADCC-mediating FcγRIIIa receptor (28,32) within the macaque population used in the studies could have affected mAb potency. A polymorphism in approximately half of humans (32) has been shown to affect ADCC and tumor-cell killing by the FDA-approved mAb, rituximab (33).…”

Section: Discussionmentioning

confidence: 99%

“…Alternatively, because ADCC is an important mechanism of action for these mAbs (23), polymorphisms of the ADCC-mediating FcγRIIIa receptor (28,32) within the macaque population used in the studies could have affected mAb potency. A polymorphism in approximately half of humans (32) has been shown to affect ADCC and tumor-cell killing by the FDA-approved mAb, rituximab (33). Although less well-characterized, three FcγRIIIa polymorphisms have been reported in macaques (34,35), and in one study, 33% (n = 9) of macaques had a FcγRIIIa polymorphism (35).…”

Section: Discussionmentioning

confidence: 99%

Delayed treatment of Ebola virus infection with plant-derived monoclonal antibodies provides protection in rhesus macaques

Olinger

Pettitt

Kim

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

353

344

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Filovirus infections can cause a severe and often fatal disease in humans and nonhuman primates, including great apes. Here, three anti-Ebola virus mouse/human chimeric mAbs (c13C6, h-13F6, and c6D8) were produced in Chinese hamster ovary and in whole plant (Nicotiana benthamiana) cells. In pilot experiments testing a mixture of the three mAbs (MB-003), we found that MB-003 produced in both manufacturing systems protected rhesus macaques from lethal challenge when administered 1 h postinfection. In a pivotal followup experiment, we found significant protection (P < 0.05) when MB-003 treatment began 24 or 48 h postinfection (four of six survived vs. zero of two controls). In all experiments, surviving animals that received MB-003 experienced little to no viremia and had few, if any, of the clinical symptoms observed in the controls. The results represent successful postexposure in vivo efficacy by a mAb mixture and suggest that this immunoprotectant should be further pursued as a postexposure and potential therapeutic for Ebola virus exposure.passive immunization | therapy

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“…Of note, NKG2C bright NK cell expansions, as well as their dominance in the Ab-dependent cytokine response, was observed in individuals with different CD16 (158V/F) genotypes regardless of their reported influence on Ab binding and Ab-mediated ADCC (52,53). Whether the frequency of NKG2C bright NK cells, not appreciated through genetic analysis, could explain the controversial data in studies addressing the impact of those polymorphisms in clinical contexts such as Ab-based anticancer therapies deserves attention (54).…”

Section: Differentiation Of Nkg2c Bright Nk Cells As Cytokine Producementioning

confidence: 99%

Antibody-Mediated Response of NKG2Cbright NK Cells against Human Cytomegalovirus

Costa‐García

Vera

Moraru³

et al. 2015

The Journal of Immunology

105

108

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Human CMV (HCMV) infection promotes a variable and persistent expansion of functionally mature NKG2Cbright NK cells. We analyzed NKG2Cbright NK cell responses triggered by Abs from HCMV+ sera against HCMV-infected MRC5 fibroblasts. Specific Abs promoted the degranulation (i.e., CD107a expression) and the production of cytokines (TNF-α and IFN-γ) by a significant fraction of NK cells, exceeding the low natural cytotoxicity against HCMV-infected targets. NK cell–mediated Ab-dependent cell-mediated cytotoxicity was limited by viral Ag availability and HLA class I expression on infected cells early postinfection and increased at late stages, overcoming viral immunoevasion strategies. Moreover, the presence of specific IgG triggered the activation of NK cells against Ab-opsonized cell-free HCMV virions. As compared with NKG2A+ NK cells, a significant proportion of NKG2Cbright NK cells was FcεR γ-chain defective and highly responsive to Ab-driven activation, being particularly efficient in the production of antiviral cytokines, mainly TNF-α. Remarkably, the expansion of NKG2Cbright NK cells in HCMV+ subjects was related to the overall magnitude of TNF-α and IFN-γ cytokine secretion upon Ab-dependent and -independent activation. We show the power and sensitivity of the anti-HCMV response resulting from the cooperation between specific Abs and the NKG2Cbright NK-cell subset. Furthermore, we disclose the proinflammatory potential of NKG2Cbright NK cells, a variable that could influence the individual responses to other pathogens and tumors.

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FcγRIIIa-158V/F polymorphism influences the binding of IgG by NK cell FcγRIIIa, independent of the FcγRIIIa-48L/R/H phenotype

Cited by 209 publications

References 0 publications

Macrophages and Fc-receptor interactions contribute to the antitumour activities of the anti-CD40 antibody SGN-40

Macrophages and Fc-receptor interactions contribute to the antitumour activities of the anti-CD40 antibody SGN-40

Delayed treatment of Ebola virus infection with plant-derived monoclonal antibodies provides protection in rhesus macaques

Antibody-Mediated Response of NKG2Cbright NK Cells against Human Cytomegalovirus

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