Synthetic allergen design reveals the significance of moderate affinity epitopes in mast cell degranulation

Michael W. Handlogten, Tanyel Kiziltepe, Nathan J. Alves, Basar Bilgicer

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

This study describes the design of a well-defined homotetravalent synthetic allergen (HTA) system to investigate the effect of hapten-IgE interactions on mast cell degranulation. A library of DNP variants with varying affinities for IgEDNP was generated (Kd from 8.1 nM to 9.2 μM), and 8 HTAs spanning this range were synthesized via conjugation of each DNP variant to the tetravalent scaffold. HTAs with hapten Kd < 235 nM stimulated degranulation following a bell-shaped dose response curve with maximum response occurring near the hapten Kd. HTAs with hapten Kd ≥ 235 nM failed to stimulate degranulation. To mimic physiological conditions, the percent of allergen specific IgE on cell surface was varied, and maximum degranulation occurred at 25% IgEDNP. These results demonstrated that moderate hapten-IgE affinities are sufficient to trigger mast cell degranulation. Moreover, this study established the HTA design as a well-defined, controllable, and physiologically relevant experimental system to elucidate the mast cell degranulation mechanism.

Original languageEnglish (US)
Pages (from-to)1796-1801
Number of pages6
JournalACS chemical biology
Volume7
Issue number11
DOIs
StatePublished - Nov 16 2012
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

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