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

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

Research output: Contribution to journalArticle

13 Citations (Scopus)

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

Fingerprint

Cell Degranulation
Haptens
Mast Cells
Allergens
Epitopes
Immunoglobulin E
Scaffolds
Libraries

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

Cite this

Synthetic allergen design reveals the significance of moderate affinity epitopes in mast cell degranulation. / Handlogten, Michael W.; Kiziltepe, Tanyel; Alves, Nathan; Bilgicer, Basar.

In: ACS Chemical Biology, Vol. 7, No. 11, 16.11.2012, p. 1796-1801.

Research output: Contribution to journalArticle

Handlogten, Michael W. ; Kiziltepe, Tanyel ; Alves, Nathan ; Bilgicer, Basar. / Synthetic allergen design reveals the significance of moderate affinity epitopes in mast cell degranulation. In: ACS Chemical Biology. 2012 ; Vol. 7, No. 11. pp. 1796-1801.
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