Humanized mAb H22 binds the human high affinity Fc receptor for IgG (FcγRI), blocks phagocytosis, and modulates receptor expression

Wallace, Paul K.; Keler, Tibor; Coleman, Kimberly D.; Vitale, Laura; Graziano, Robert F.; Guyre, Paul M.; Fanger, Michael W.

doi:10.1002/jlb.62.4.469

Cited by 29 publications

(26 citation statements)

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“…31 and data not shown), which do not bind antiFc␥RI constructs. This is in accordance with modulation studies by Wallace et al (24), which demonstrated the specificity of H22 for Fc␥RI. Furthermore, Fc␥RI modulation in our studies was not blocked by Abs to irrelevant cell surface receptors, Fc␥RII or CD11b (data not shown), suggesting that those two molecules did not take part in anti-Fc␥RI-mediated modulation of Fc␥RI.…”

Section: Discussionsupporting

confidence: 93%

“…We also explored the contribution of the relative level of receptor expression and the presence of ligand on modulation. Our findings suggest that trivalent anti-Fc␥RI constructs modulate Fc␥RI in the absence of IgG in a concentration-dependent manner similar to the modulation of monocyte Fc␥RI reported by Wallace et al (24), although the kinetics of modulation are more rapid on 10.6 cells. However, the presence of IgG leads to greater modulation at higher concentrations of modulator and permits the internalization of non-crosslinked anti-Fc␥RI constructs.…”

supporting

confidence: 89%

“…This is similar to what has been found in studies by others using U937 cells, which showed internalization to occur within 5 min after cross-linking receptorbound IgG (25). In studies by Wallace et al (24), Fc␥RI modulation on normal human monocytes was evident at 2 h and maximal at 8 h when H22 was used as modulator. The differences in kinetics observed in that study vs ours could be due to the nature of the cell populations studied, as well as the fact that freshly isolated monocytes are likely to have residual bound IgG, which can alter modulation kinetics.…”

Section: Discussionmentioning

confidence: 94%

“…Furthermore, the down-modulation of surface Fc␥RI by mAb H22 was shown to be concentrationdependent, such that 0.1 g/ml of H22 was optimal and lower or higher concentrations were less effective (24). It has been demonstrated that Fc␥RI recycles into and out of the cell when ligand is bound, and that the addition of an anti-Fc␥RI Ab which binds outside the ligand-binding site causes receptors to accumulate inside the cell and not recycle to the cell surface (25).…”

mentioning

confidence: 99%

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Receptor Modulation by FcγRI-Specific Fusion Proteins Is Dependent on Receptor Number and Modified by IgG

Guyre

Keler²,

Swink³

et al. 2001

The Journal of Immunology

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The high-affinity IgG receptor, FcγRI (CD64), is constitutively expressed exclusively on professional APCs. Human FcγRI binds monomeric IgG with high affinity and is, therefore, saturated in vivo. The binding of IgG to FcγRI causes receptor recycling, while Abs that cross-link FcγRI cause rapid down-modulation of surface FcγRI. Because studies performed in the absence of ligand may not be representative of FcγRI modulation in vivo, we investigated the ability of FcγRI-cross-linking Abs and non-cross-linking derivatives to modulate FcγRI in the presence and absence of ligand. In the absence of ligand mAb H22 and wH22xeGFP, an enhanced green fluorescent protein (eGFP)-labeled fusion protein of H22, cross-linked and rapidly down-modulated surface FcγRI on the human myeloid cell line, U937, and its high FcγRI-expressing subclone, 10.6. This effect was dependent on the concentration of fusion protein and the level of FcγRI expression and correlated with internalization of both wH22xeGFP and FcγRI, itself, as assessed by confocal microscopy. A single-chain Fv version, sFv22xeGFP, which does not cross-link FcγRI, was unable to modulate FcγRI in the absence of IgG. However, if ligand was present, treatment with either monovalent or cross-linking fusion protein led to intracellular receptor accumulation. These findings suggest at least two alternate mechanisms of internalization that are influenced by ligand and demonstrate the physiologic potential of FcγRI to transport a large antigenic load into APCs for processing. These studies may lead to the development of better FcγRI-targeted vaccines, as well as therapies to down-modulate FcR involved in autoimmune diseases.

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Section: Discussionsupporting

confidence: 93%

supporting

confidence: 89%

Section: Discussionmentioning

confidence: 94%

mentioning

confidence: 99%

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Receptor Modulation by FcγRI-Specific Fusion Proteins Is Dependent on Receptor Number and Modified by IgG

Guyre

Keler²,

Swink³

et al. 2001

The Journal of Immunology

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“…PBLs were depleted of granulocytes and RBCs by Ficoll density centrifugation. Monocyte depletion, when done, was accomplished by cold aggregation performed by Joseph D. Tario of the Roswell Park Flow Cytometry Facility (15).…”

Section: Patient Samplesmentioning

confidence: 99%

Reciprocal Functional Modulation of the Activation of T Lymphocytes and Fibroblasts Derived from Human Solid Tumors

Barnas

Simpson-Abelson

Brooks

et al. 2010

The Journal of Immunology

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Fibroblasts are a dominant cell type in most human solid tumors. The possibility that fibroblasts have the capacity to interact with and modulate the function of tumor-associated T lymphocytes makes them a potential therapeutic target. To address this question, primary cultures of fibroblasts derived from human lung tumors were established and cultured with T cells derived from the same tumor. The tumor fibroblasts significantly enhance the production of IFN-γ and IL-17A by the tumor-associated T cells following a CD3/CD28-induced activation of the T cells. This enhancement was fibroblast cell dose-dependent and did not require direct contact between the two cell types. Tumor-associated fibroblast-conditioned media similarly enhanced both IFN-γ and IL-17A in activated T cells, and this enhancement was significantly reduced by Abs to IL-6. Conditioned media derived from activated lymphocyte cultures significantly enhanced IL-6 production by tumor fibroblasts. A similar enhancement of IFN-γ and IL-17A was observed when activated T cells from a normal donor were cultivated with skin fibroblasts derived from the same donor. These results establish that fibroblasts and autologous lymphocytes, whether derived from the tumor microenvironment or from nonmalignant tissues, have the capacity to reciprocally interact and modulate function. In contrast to other reports, fibroblasts are shown to have an immunostimulatory effect upon activated T lymphocytes. The ability of fibroblasts to enhance two T cell cytokines known to have an impact upon tumor progression suggests that fibroblasts play an important role in tumor pathogenesis that could be exploited therapeutically.

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Editorial

Aliabadi

Gatmin

Sellier

2008

Commun. Numer. Meth. Engng.

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Owing to a technical problem in the submission process, selected presentations from the 7th International Conference on Boundary Elements, which took place in Paris, France, in September 2006 (http://beteq.engineeringconferences.net/), will not be published in a separate special issue. Links to these papers as they were published in the journal are listed at the end of this editorial. Copyright © 2008 John Wiley & Sons, Ltd.

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Humanized mAb H22 binds the human high affinity Fc receptor for IgG (FcγRI), blocks phagocytosis, and modulates receptor expression

Abstract: Abstract:About

Cited by 29 publications

References 1 publication

Receptor Modulation by FcγRI-Specific Fusion Proteins Is Dependent on Receptor Number and Modified by IgG

Receptor Modulation by FcγRI-Specific Fusion Proteins Is Dependent on Receptor Number and Modified by IgG

Reciprocal Functional Modulation of the Activation of T Lymphocytes and Fibroblasts Derived from Human Solid Tumors

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