IgE occupancy and antigen valency cooperate to control FcεRI aggregation geometry and signaling efficiency.

ABSTRACT: The crosslinking of IgE-bound FcεRI by multivalent allergens initiates mast cell and basophil signaling underlying Type 1 allergy. Yet, how allergen properties and IgE occupancy impact receptor aggregation and downstream signaling remain unclear. We used Phl p 1-specific IgE and recombinant fusion proteins presenting a Phl p 1-derived peptide in defined valencies and positions (MB1N, MB2N, MB4N, MB1N1C) to probe antigen-dependent signaling. Tetravalent MB4N evoked stronger degranulation and Ca2+ response than bivalent antigens, MB2N and MB1N1C. MB4N was also capable of signaling at low IgE occupancy and in Lyn-deficient cells. Monte Carlo simulations predicted that MB4N forms larger, complex receptor aggregates, while MB2N and MB1N1C produce dimers and linear chains. Consistently, addition

SUBMITTER: Linhart B 

PROVIDER: S-EPMC12636472 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature