title: Synthetic allergen design reveals the significance of moderate affinity epitopes in mast cell degranulation.
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 IgE(DNP) was generated (K(d) 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 K(d) < 235 nM stimulated degranulation following a bell-shaped dose response curve with maximum response occurring near the hapten K(d). HTAs with hapten K(d) ≥ 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% IgE(DNP). 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.
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, Indiana 46556, United States.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Handlogten
authors.forename: Tanyel
authors.initials: T
authors.lastname: Kiziltepe
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Alves
authors.forename: Basar
authors.initials: B
authors.lastname: Bilgicer
mesh_terms: D000485:Allergens / Q000737:chemistry / Q000276:immunology*; D000818:Animals; D000915:Antibody Affinity; D015550:Cell Degranulation; D002460:Cell Line; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D006241:Haptens / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology / Q000502:physiology*
chemical_list: D000485:Allergens; D000939:Epitopes; D006241:Haptens; D007073:Immunoglobulin E