Mechanism of binding of multivalent immune complexes to Fc receptors. 1. Equilibrium binding

Dower, Steven K.; DeLisi, Charles; Titus, Julie A.; Segal, David M.

doi:10.1021/bi00525a007

Cited by 93 publications

(56 citation statements)

References 41 publications

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“…It should be noted that the best fit obtained by Scatchard-type analysis of the present binding isotherms was represented by a straight line, in agreement with another study published previously (31). In a multivalent system, this behavior can be explained by self-association ofthe bound oligomers on the platelet surface (30). Variations in this regard, possibly owing to differences in the ligand and platelets used, may explain why others (2) have observed the curvilinear Scatchard plots predicted in a simple multivalent system.…”

Section: Discussionsupporting

confidence: 92%

Distinct abnormalities in the interaction of purified types IIA and IIB von Willebrand factor with the two platelet binding sites, glycoprotein complexes Ib-IX and IIb-IIIa.

Marco¹,

Mazzucato²,

Roia³

et al. 1990

J. Clin. Invest.

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IntroductionWe have studied the interaction of the congenitally abnormal type IIA and IIB von Willebrand factor (vWF) molecules, both lacking the larger multimeric forms, with the two vWF binding sites on platelets, the glycoprotein (GP) Ib-IX and GP (8); in the latter, vWF has increased affinity for platelets and, consequently, the larger multimers are removed from the circulation as a result ofplatelet binding (7, 9-1 1). To date, however, there is no detailed information on the modalities of interaction of IIA and IIB vWF with the corresponding binding sites on platelets. The association of vWF with both GP Ib-IX and GP IlbIla appears to be important in thrombus formation (12, 13), and knowledge ofthe molecular mechanisms responsible for it is likely to provide useful information for understanding the processes involved in normal hemostasis as well as pathological vascular occlusion. In this regard, the study of molecular variants of von Willebrand disease is of particular interest if the existence of specific molecular defects can be correlated to relevant abnormalities of interaction with platelets. To address these issues, we have purified the congenitally abnormal vWF molecule from the plasma of patients with type IIA and IIB von Willebrand disease, and evaluated in a quantitative manner the interaction with GP Ib-IX and GP Ib-IhIIa. Our findings demonstrate that IIB vWF can bind to GP Ib-IX in the absence of any mediating or activating molecule, suggesting the existence of a molecular defect resulting in increased affinity for this platelet site. Such increased affinity is also evident in the presence of ristocetin, in spite of the absence of larger multimers. In contrast, IIA vWF interacts with GP Ib-IX with extremely reduced affinity. The severity of this abnormality may reflect the existence of specific structural alterations af-

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Section: Discussionsupporting

confidence: 92%

Distinct abnormalities in the interaction of purified types IIA and IIB von Willebrand factor with the two platelet binding sites, glycoprotein complexes Ib-IX and IIb-IIIa.

Marco¹,

Mazzucato²,

Roia³

et al. 1990

J. Clin. Invest.

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“…The equilibrium of IgE binding to Fc⑀RI was determined by incubating 5 ϫ 10 5 RBL-2H3 cells with 25 ng 125 I-mIgE for the indicated amount of time. A fraction of the cells was spun over phlatate oil (26) to determine the amount of IgE bound. The cpm bound was adjusted for nonspecific binding by subtracting the cpm of cells incubated with a 100-fold excess cold mIgE.…”

Section: I-ige Binding Analysismentioning

confidence: 99%

Temperature Effect on IgE Binding to CD23 Versus FcεRI

Chen

Kilmon

et al. 2003

The Journal of Immunology

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A chimeric soluble CD23, consisting of the extracellular domain of mouse CD23 and a modified leucine zipper (lz-CD23), has been shown to inhibit IgE binding to the FcεRI. A similar human CD23 construct was also shown to inhibit binding of human IgE to human FcεRI. In both systems, the inhibition was found to be temperature dependent; a 10-fold molar excess of lz-CD23 gave 90–98% inhibition at 4°C, dropping to 20–30% inhibition at 37°C. Surface plasmon resonance analysis of lz-CD23 binding to an IgE-coated sensor chip suggested that the effective concentration of lz-CD23 was lower at the higher temperatures. Analysis of 125I-IgE binding to CD23+-Chinese hamster ovary cells also indicated that increased temperature resulted in a lower percentage of IgE capable of interacting with CD23. In contrast, IgE interacts more effectively with FcεRI+-rat basophilic leukemia cells at 37°C compared with 4°C. The results support the concept that the open and closed IgE structures found by crystallography interact differently with the two IgE receptors and suggest that temperature influences the relative percentage of IgE in the respective structural forms. Changes in CD23 oligomerization also plays a role in the decreased binding seen at physiological temperatures.

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“…Scatchard analysis of the data yielded a curvilinear plot at both temperatures . The curves passing through the points have been fit with an equation consisting of the sum of two Michaelis-Menten terms (30) . Direct measurement of the binding affinity of unlabeled IL-7 by inhibition of binding of 125 1-IL-7 to IxN/2b cells at 37°C is shown in Fig.…”

Section: Ndmentioning

confidence: 99%

“…Curvilinear equilibrium binding data were analyzed using an equation consisting of the sum of two simple Michaelis-Menten terms as previously described (18,30) . Inhibition data were analyzed with an equation for competitive inhibition between two ligands for two types of sites that consists of the sum of two simple terms as described elsewhere (18) .…”

mentioning

confidence: 99%

Murine interleukin 7 (IL-7) receptor. Characterization on an IL-7-dependent cell line.

Park

Friend

Schmierer

et al. 1990

The Journal of Experimental Medicine

137

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A murine cell line (IxN/2b) absolutely dependent upon exogenous IL-7 for continued growth has been obtained that expresses lymphoid precursor and class I MHC antigens and also contains a rearranged mu heavy chain. This cell line has been used to define the binding and structural characteristics of the murine IL-7 receptor using 125I-labeled recombinant murine IL-7. 125I-IL-7 binding to IxN/2b cell was rapid and saturable at both 4 degrees and 37 degrees C. Equilibrium binding studies produced curvilinear Scatchard plots at both temperatures with high and low affinity Ka values of approximately 1 x 10(10) M-1 and 4 x 10(8) M-1, respectively, and a total of 2,000-2,500 IL-7 binding sites expressed per cell. Experiments measuring inhibition of binding of 125I-IL-7 by unlabeled IL-7 also produced data consistent with the existence of two classes of IL-7 receptors. Evidence concerning the possible molecular nature of two classes of IL-7 receptors was provided by dissociation kinetics and affinity crosslinking experiments. The dissociation rate of 125I-IL-7 was markedly increased when measured in the presence of unlabeled IL-7 at both 37 degrees and 4 degrees C, which is diagnostic of a receptor population displaying negative cooperativity. Crosslinking studies showed that under both reducing and nonreducing conditions, the major crosslinked species observed corresponded to a receptor size of 75-79 kD while a less intense higher molecular mass crosslinked species was also seen which corresponded to a receptor size approximately twice as large (159-162 kD). Both types of experiments suggest that the IL-7 receptor may form noncovalently associated dimers in the membrane. The IL-7 receptor was expressed on pre-B cells, but not detected on several murine B cell lines or primary mature B cells. It was also expressed on murine thymocytes, some T lineage cell lines, and on bone marrow-derived macrophage. All cells binding 125I-IL-7 exhibited curvilinear Scatchard plots. No cytokines or growth factors tested were able to inhibit binding of 125I-IL-7 to its receptor. These results define the initial binding and structural characteristics, and the cellular distribution, of the murine IL-7 receptor.

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Mechanism of binding of multivalent immune complexes to Fc receptors. 1. Equilibrium binding

Cited by 93 publications

References 41 publications

Distinct abnormalities in the interaction of purified types IIA and IIB von Willebrand factor with the two platelet binding sites, glycoprotein complexes Ib-IX and IIb-IIIa.

Distinct abnormalities in the interaction of purified types IIA and IIB von Willebrand factor with the two platelet binding sites, glycoprotein complexes Ib-IX and IIb-IIIa.

Temperature Effect on IgE Binding to CD23 Versus FcεRI

Murine interleukin 7 (IL-7) receptor. Characterization on an IL-7-dependent cell line.

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