| Design of a heterotetravalent synthetic allergen that reflects epitope heterogeneity and IgE antibody variability to study mast cell degranulation. | |
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MedLine Citation:
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PMID: 23050868 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The present paper describes the design of a HtTA (heterotetravalent allergen) as a multi-component experimental system that enables an integrative approach to study mast cell degranulation. The HtTA design allows presentation of two distinct haptens, each with a valency of 2, thereby better reflecting the complexity of natural allergens by displaying epitope heterogeneity and IgE antibody variability. Using the HtTA design, synthetic allergens HtTA-1 and HtTA-2 were synthesized to model a combination of epitope/IgE affinities. HtTA-1 presented DNP (2,4-dinitrophenyl) and dansyl haptens (Kd=22 and 54 nM for IgEDNP and IgEdansyl respectively) and HtTA-2 presented dansyl and the weak-affinity DNP-Pro (DNP-proline) haptens (Kd=550 nM for IgEDNP). Both HtTAs effectively induced degranulation when mast cells were primed with both IgEDNP and IgEdansyl antibodies. Interestingly tetravalent DNP-Pro or bivalent dansyl were insufficient in stimulating a degranulation response, illustrating the significance of valency, affinity and synergy in allergen-IgE interactions. Importantly, maximum degranulation with both HtTA-1 and HtTA-2 was observed when only 50% of the mast cell-bound IgEs were hapten-specific (25% IgEdansyl and 25% IgEDNP). Taken together, results of the present study establish the HtTA system as a physiologically relevant experimental model and demonstrates its utility in elucidating critical mechanisms of mast cell degranulation. |
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Authors:
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Michael W Handlogten; Tanyel Kiziltepe; Basar Bilgicer |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: The Biochemical journal Volume: 449 ISSN: 1470-8728 ISO Abbreviation: Biochem. J. Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2012-12-10 Completed Date: 2013-02-08 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 2984726R Medline TA: Biochem J Country: England |
Other Details:
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Languages: eng Pagination: 91-9 Citation Subset: IM |
Affiliation:
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Department of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, IN 46556, U.S.A. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Allergens
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chemistry,
immunology*,
physiology Animals Cell Degranulation / drug effects, physiology* Drug Design* Epitopes / chemistry*, immunology* Genetic Heterogeneity Immunoglobulin E / biosynthesis*, chemistry Mast Cells / drug effects, immunology*, metabolism* Rats |
| Grant Support | |
ID/Acronym/Agency:
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R03 AI085485/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Allergens; 0/Epitopes; 37341-29-0/Immunoglobulin E |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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