Document Detail


Design of a heterotetravalent synthetic allergen that reflects epitope heterogeneity and IgE antibody variability to study mast cell degranulation.
MedLine Citation:
PMID:  23050868     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Michael W Handlogten; Tanyel Kiziltepe; Basar Bilgicer
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  The Biochemical journal     Volume:  449     ISSN:  1470-8728     ISO Abbreviation:  Biochem. J.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2012-12-10     Completed Date:  2013-02-08     Revised Date:  2014-01-09    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  England    
Other Details:
Languages:  eng     Pagination:  91-9     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Allergens / 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:
R03 AI085485/AI/NIAID NIH HHS; R03 AI085485/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Allergens; 0/Epitopes; 37341-29-0/Immunoglobulin E
Comments/Corrections

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