Biologic function of the Fc fragments of E myeloma protein
TL;DR: The results suggested that structural changes in the Fc portion of γE molecules initiate enzymatic sequences leading to the release of the chemical mediators in E myeloma protein PS.
About: This article is published in Immunochemistry.The article was published on 1970-08-01. It has received 146 citations till now. The article focuses on the topics: Fragment crystallizable region & Papain.
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TL;DR: The structural analysis of the functional basis of FcγR and FCɛR signaling is beginning to shed some light on the way these receptors trigger biological responses, and the molecular dissection of the pathways involved in signaling is also underway.
Abstract: Publisher Summary This chapter focuses on studies of the murine and human leukocyte FcγR and FCɛR I, with particular reference to the structural characterization of these receptors, the molecular nature of their interaction with immunoglobulin (Ig), and their mechanisms of signal transduction. In addition, the chapter also reviews different aspects of FcμR, FcαR, the poly Ig receptor, the receptor for the transport of Ig in neonatal gut, and receptors for IgD. The characterization of the proteins, transcripts, and genes of the different classes of both these FcR families— FcγR and FCɛR I—has largely been completed and those for IgM, IgD, and IgA receptors still to be completed. Attention is now turning to understanding the nature of the mechanisms by which these receptors and their subunits are able to mediate their functions. The structural analysis of the functional basis of FcγR and FCɛR signaling is beginning to shed some light on the way these receptors trigger biological responses, and the molecular dissection of the pathways involved in signaling is also underway. The understanding of these interactions may provide the means to devise strategies to inhibit pathophysiological effects of FcR function that would have far reaching implications in the treatment of antibody induced hypersensitivity.
537 citations
TL;DR: The results of the study suggest that IgE-allergen interaction on the surfaces of mast cells or on infiltrating basophils causes both immediate and late cutaneous responses.
Abstract: IgE antibodies are usually thought to induce only immediate skin reactions. We have shown that the intradermal injection of a number of different allergens can produce a prolonged inflammatory reaction after the immediate wheal and flare in most sensitive subjects. This late inflammatory response occurs 6-12 h after challenge and is characterized by diffuse edema, erythema, pruritus, and heat. Both immediate and late responses can also be seen after passive sensitization of skin sites in nonatopic subjects. That IgE is involved in inducing the reaction was shown by the abolition of both immediate and late responses by passive transfer tests in the following experiments: (a) heating atopic serum at 56degreesC for 4 h, (b) removing IgE from the atopic serum by a solid phase anti-IgE immunoabsorbent, and (c) competitively inhibiting the binding of IgE antibodies to cells by an IgE myeloma protein. In addition, both responses were induced by affinity chromatography-purified IgE antibody, followed by antigenic challenge. Very similar lesions could also be induced by intradermal injection of Compound 48/80, thus suggesting a central role in the reaction for the mast cell or basophil. Histologically, the late phase is characterized by edema and a mixed cellular infiltration, predominantly lymphocytic but also containing eosinophils, neutrophils and basophils. Direct immunofluorescent staining did not show deposition of immunoglobulins or complement components, except IgM in 2 of 15 and C3 in 1 of 15 patients. This finding indicates that the late phase does not depend on the deposition of immune complexes. The results of the study suggest that IgE-allergen interaction on the surfaces of mast cells or on infiltrating basophils causes both immediate and late cutaneous responses.
505 citations
TL;DR: A cDNA clone encoding the human lymphocyte receptor for IgE (Fc epsilon R) is isolated and shows striking sequence homology with chicken asialoglycoprotein receptor (hepatic lectin), suggesting a possible role for Fc ePSilon R in endocytosis.
353 citations
TL;DR: Sequence analysis of the cloned cDNAs revealed that these Fc epsilon RII species appear to be generated utilizing different transcriptional initiation sites and alternative RNA splicing, which may explain the difference in Fc wtihin B cells and the effector phase of IgE-mediated immunity.
325 citations
TL;DR: The reaction mechanism appears to consist of a simple reversible binding reaction with k 1 = 9.6 x 104 M–1 sec–1 and k –1 ⩽ 1.8 kcal/mol, and the calculated KA is therefore ⩾ 6 x 109 M-1.
Abstract: Previous studies indicated that cultured rat basophilic leukemia cells have surface receptors which bind IgE with high specificity. In this paper we describe some quantitative aspects of the phenomenon. The reaction mechanism appears to consist of a simple reversible binding reaction with k1 = 9.6 x 104 M–1 sec–1 and k–1 ⩽ 1.6 x 10–5 sec–1 at 37°C. The calculated KA is therefore ⩾ 6 x 109 M–1. The activation energy of binding was found to be 7.8 kcal/mol. The number of binding sites/cell varied between 3 x 105 to over 1 x 106. The binding was insensitive to pH's between 6–8 but at pH 3.0 complete dissociation of bound IgE occurred in ∼ 1 min at 0°C leaving the receptors for IgE intact. Ca++ plus EDTA and Mg++ plus EDTA produce a fairly marked reduction in binding capacity though these reagents alone produce much smaller effects.
297 citations
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References
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TL;DR: By standardizing the technical conditions of the experiment it is possible to use this principle for the immunochemical determination of antigens, and the lower limit of the method was found to correspond to 0·0025 μg of antigen, and to an antigen concentrations of 1·25 μg per ml.
8,937 citations
TL;DR: The results are similar to those of previous studies, where the objective was to establish a cause-and-effect relationship, rather than a straightforward relationship between the number of cells and the content of the molecule.
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