IgG-binding properties of novel bacterial Fc-receptor pH6 antigen (PsaA protein) Yersinia pestis

We describe a method for synchronously assembling antigen-antibody complexes underneath macrophages adherent to an antigen-coated surface. We have used this method to study the mechanism of Fc receptor (FcR) disappearance that occurs when resident and thioglycollate-elicited mouse macrophages are cultured on immune complex-coated surfaces. Erythrocytes opsonized with IgG (E(IgG) and a monoclonal antibody (2.4G2 IgG) directed against the trypsin-resistant FcR (FcRII) were used as indicators of the presence and distribution of FcRII molecules on the macrophage plasma membrane. Inhibitors of aerobic (NaCN) and anerobic (2-deoxyglucose, NaF) glycolysis and pinocytosis, of protein biosynthesis (cycloheximide), and of cytoskeletal function (cytochalasin B and D, colchicine, podophyllotoxin, taxol) did not reduce the rate or extent of FcRII modulation. Moreover, treatment of the macrophages with 0.1-0.5% formaldehyde did not reduce the extent of FcRII modulation as measured by the disappearance of E(IgG) binding sites. FcRII modulation was markedly slowed when the temperature was decreased to 2-4 degrees C. These results prove that FcRII modulation is governed by diffusion of the receptor in the plasma membrane. From the speed of FcRII disappearance from the macrophage's upper surface we calculate that the receptor has a diffusion coefficient at 37 degrees C of 2.5 X 10(-9) cm2/s. This finding indicates that FcRII, in its unligated form, is not linked to the macrophage's cytoskeleton, and that the receptor is capable of accommodating spatially to any distribution of ligands on a particle's surface.

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A Naturally Occurring Mutation in FcγRIIA: A Q to K127 Change Confers Unique IgG Binding Properties to the R131 Allelic Form of the Receptor

Blood ◽

10.1182/blood.v91.2.656 ◽

1998 ◽

Vol 91 (2) ◽

pp. 656-662 ◽

Cited By ~ 25

Author(s):

Cynthia F. Norris ◽

Luminita Pricop ◽

Sean S. Millard ◽

Scott M. Taylor ◽

Saul Surrey ◽

...

Keyword(s):

Disease Susceptibility ◽

Screening Methods ◽

Allelic Form ◽

Fcγ Receptors ◽

Binding Properties ◽

Naturally Occurring ◽

Igg Binding ◽

Polymorphic Forms ◽

Differential Binding ◽

Therapeutic Monoclonal Antibodies

Abstract FcγRIIa is widely expressed on hematopoietic cells. There are two known allelic polymorphic forms of FcγRIIa, FcγRIIa-R131 and FcγRIIa-H131, which differ in the amino acid at position 131 in the second Ig-like domain. In contrast to FcγRIIa-R131, FcγRIIa-H131binds hIgG2 but not mIgG1, and this differential binding has clinical implications for host defense, autoimmune disease, immunohematologic disease, and response to therapeutic monoclonal antibodies. We identified a novel FcγRIIA genotype in a healthy individual homozygous for FcγRIIA R/R131 in whom a C to A substitution at codon 127 changes glutamine (Q) to lysine (K) in one of the two FcγRIIA genes. This individual's homozygosity for FcγRIIA-R/R131 leads to the prediction that the receptors on her cells would not bind hIgG2. Monocyte and neutrophil phagocytosis of hIgG2-opsonized erythrocytes was significantly higher (P < .05) for cells from this K/Q127, R/R131 individual than for Q/Q127, R/R131 donors. Platelet aggregation stimulated by an mIgG1 anti-CD9 antibody in this individual was significantly different (P < .05) from Q/Q127, H/R131 and Q/Q127, H/H131 donors and similar to Q/Q127, R/R131. Our data show that the K127/R131 receptors have a unique phenotype, binding both hIgG2 and mIgG1. Further functionally significant mutations in human Fcγ receptors and possible novel mechanisms for inherited differences in disease susceptibility should be sought with unbiased screening methods.

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The influence of a residual group in low-molecular-weight allergoids of Artemisia vulgaris pollen on their allergenicity, IgE- and IgG-binding properties

Allergy ◽

10.1034/j.1398-9995.2002.23739.x ◽

2002 ◽

Vol 57 (11) ◽

pp. 1013-1020 ◽

Cited By ~ 14

Author(s):

T. Cirkovic ◽

M. Gavrovic-Jankulovic ◽

S. Prisic ◽

R. M. Jankov ◽

L. Burazer ◽

...

Keyword(s):

Molecular Weight ◽

Low Molecular Weight ◽

Artemisia Vulgaris ◽

Binding Properties ◽

Igg Binding

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Humanized IgG1 Variants with Differential Binding Properties to the Neonatal Fc Receptor: Relationship to Pharmacokinetics in Mice and Primates

Drug Metabolism and Disposition ◽

10.1124/dmd.106.011734 ◽

2006 ◽

Vol 35 (1) ◽

pp. 86-94 ◽

Cited By ~ 99

Author(s):

Amita Datta-Mannan ◽

Derrick R. Witcher ◽

Ying Tang ◽

Jeffry Watkins ◽

Weidong Jiang ◽

...

Keyword(s):

Fc Receptor ◽

Neonatal Fc Receptor ◽

Binding Properties ◽

Differential Binding

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Surfactant protein A binds to IgG and enhances phagocytosis of IgG-opsonized erythrocytes

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00188.2006 ◽

2006 ◽

Vol 291 (6) ◽

pp. L1199-L1206 ◽

Cited By ~ 10

Author(s):

Peggy M. Lin ◽

Jo Rae Wright

Keyword(s):

Immune Complexes ◽

Protein A ◽

Surfactant Protein ◽

Fc Receptor ◽

Innate Immune ◽

Surfactant Protein A ◽

Complement Protein ◽

Calcium Dependent ◽

Igg Binding ◽

Pathogen Clearance

Surfactant protein (SP)-A and SP-D, immunoglobulins, and complement all modulate inflammation within the lung by regulating pathogen clearance. For example, SP-A binds to and opsonizes a variety of bacteria and viruses, thereby enhancing their phagocytosis by innate immune cells such as alveolar macrophages. Immunoglobulins, which bind to antigen and facilitate Fc receptor-mediated phagocytosis, can also activate complement, a family of soluble proteins with multiple host defense functions. Previous studies showed that SP-A and complement protein C1q interact. Since complement protein C1q binds to IgG and IgM immune complexes, the hypothesis tested in this study was that SP-A, which is structurally homologous to C1q, also binds to IgG and affects its functions. SP-A binds to the Fc, rather than the Fab, region of IgG. Binding is calcium dependent but not inhibited by saccharides known to bind to SP-A's carbohydrate recognition domain. The binding of SP-A does not inhibit the formation of immune complexes or the binding of IgG to C1q. In contrast, SP-A enhances the uptake of IgG-coated erythrocytes, suggesting that SP-A might be influencing Fc receptor-mediated uptake. In summary, this study shows a novel interaction between SP-A and IgG and a functional consequence of the binding.

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Binding of human and animal immunoglobulins to the IgG Fc receptor induced by human cytomegalovirus

Journal of General Virology ◽

10.1099/0022-1317-82-5-1137 ◽

2001 ◽

Vol 82 (5) ◽

pp. 1137-1145 ◽

Cited By ~ 32

Author(s):

Annika Antonsson ◽

P. J. Hugo Johansson

Keyword(s):

Human Cytomegalovirus ◽

Binding Sites ◽

Fc Receptor ◽

Lung Fibroblasts ◽

Affinity Constant ◽

Human Embryonic Lung ◽

Binding Properties ◽

Human Igg ◽

Infected Cells ◽

Simplex Virus

Human cytomegalovirus (HCMV)-infected cells express a virus-encoded receptor that is able to bind the Fc part of IgG. Some basic binding properties of this Fc receptor (FcR) have been examined. The affinity constant (K a) for human IgG Fc fragment in its interaction with acetone-fixed, HCMV-infected human embryonic lung fibroblasts was estimated to be around 2×108 M−1 and the number of binding sites was estimated to be around 2×106 per cell. Of the human IgG, IgA, IgM and IgD classes, only IgG reacted with the receptor, and all four of the IgG subclasses were reactive. IgG from rabbit, hamster, cat, swine and horse exhibited binding to the HCMV FcR, in contrast to IgG from mouse, rat, guinea pig, dog, sheep, goat, cow and chicken. Immunoglobulins with and without HCMV IgG FcR-binding properties, like IgG from rabbit and mouse, can be of value in revealing the functional importance of the receptor. When the immunoglobulins were tested against herpes simplex virus type 1-induced FcR, both similarities and differences in immunoreactivity were seen relative to the HCMV FcR, which makes it unlikely that the binding sites for these two herpesvirus FcRs on the IgG molecule are identical.

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A Naturally Occurring Mutation in FcγRIIA: A Q to K127 Change Confers Unique IgG Binding Properties to the R131 Allelic Form of the Receptor

Blood ◽

10.1182/blood.v91.2.656.656_656_662 ◽

1998 ◽

Vol 91 (2) ◽

pp. 656-662

Author(s):

Cynthia F. Norris ◽

Luminita Pricop ◽

Sean S. Millard ◽

Scott M. Taylor ◽

Saul Surrey ◽

...

Keyword(s):

Disease Susceptibility ◽

Screening Methods ◽

Allelic Form ◽

Fcγ Receptors ◽

Binding Properties ◽

Naturally Occurring ◽

Igg Binding ◽

Polymorphic Forms ◽

Differential Binding ◽

Therapeutic Monoclonal Antibodies

FcγRIIa is widely expressed on hematopoietic cells. There are two known allelic polymorphic forms of FcγRIIa, FcγRIIa-R131 and FcγRIIa-H131, which differ in the amino acid at position 131 in the second Ig-like domain. In contrast to FcγRIIa-R131, FcγRIIa-H131binds hIgG2 but not mIgG1, and this differential binding has clinical implications for host defense, autoimmune disease, immunohematologic disease, and response to therapeutic monoclonal antibodies. We identified a novel FcγRIIA genotype in a healthy individual homozygous for FcγRIIA R/R131 in whom a C to A substitution at codon 127 changes glutamine (Q) to lysine (K) in one of the two FcγRIIA genes. This individual's homozygosity for FcγRIIA-R/R131 leads to the prediction that the receptors on her cells would not bind hIgG2. Monocyte and neutrophil phagocytosis of hIgG2-opsonized erythrocytes was significantly higher (P < .05) for cells from this K/Q127, R/R131 individual than for Q/Q127, R/R131 donors. Platelet aggregation stimulated by an mIgG1 anti-CD9 antibody in this individual was significantly different (P < .05) from Q/Q127, H/R131 and Q/Q127, H/H131 donors and similar to Q/Q127, R/R131. Our data show that the K127/R131 receptors have a unique phenotype, binding both hIgG2 and mIgG1. Further functionally significant mutations in human Fcγ receptors and possible novel mechanisms for inherited differences in disease susceptibility should be sought with unbiased screening methods.

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IgG binding of mugwort pollen allergens and allergoids exposed to simulated gastrointestinal conditions measured by a self-developed ELISAtest

Journal of the Serbian Chemical Society ◽

10.2298/jsc0407533p ◽

2004 ◽

Vol 69 (7) ◽

pp. 533-540 ◽

Cited By ~ 3

Author(s):

Natalija Polovic ◽

Tanja Cirkovic-Velickovic ◽

Marija Gavrovic-Jankulovic ◽

Lidija Burazer ◽

Danica Djergovic-Petrovic ◽

...

Keyword(s):

Prolonged Exposure ◽

Binding Potential ◽

Pollen Extract ◽

Artemisia Vulgaris ◽

Pollen Allergens ◽

Binding Properties ◽

Gastrointestinal Conditions ◽

Igg Binding ◽

Specific Igg ◽

Acidic Conditions

This study considers the influence of exposure to simulated gastrointestinal conditions (saliva, gut, intestine and acidic conditions of the gut) on IgG binding of unmodified allergens and three types of LMW allergoids of Artemisia vulgaris pollen extract obtained by means of potassium cyanate succinic and maleic anhydride. It also concerns the optimization of a self-developed ELISA assay for comparison of the specific IgG binding of mugwort pollen extract and modified mugwort pollen derivatives. The ELISA was conducted with a mugwort pollen extract coupled to the plate, using the sera from 12 mugwort- pollen allergic patients. The exposure to saliva fluid for 2 min did not influence the IgG binding properties of allergens and allergoids. Exposure of mugwort pollen allergens and LMW allergoids to the acidic conditions of the gut did not dramatically change their IgG binding properties. By exposing mugwort pollen extract and LMW derivatives to the SGF conditions for 1 h, the percent of IgG binding epitopes was reduced to a half of its starting value in the extract and to about 30%in all the allergoid samples. After prolonged exposure only the carbamyl derivative showed reduced IgG binding. Changes of the IgG binding potential of all four samples after exposure in SIF followed a similar pattern.

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