IgE-mediated allergen presentation via Fc epsilon RI on antigen-presenting cells

In atopic individuals, cutaneous antigen-presenting cells (APC), i.e. Langerhans' cells (LC) and dermal dendritic cells (DDC), frequently display anti-IgE reactivity. While earlier observations suggested that this phenomenon results from the binding of (complexed) IgE to the low affinity IgE receptor (Fc epsilonRII/CD23), recent evidence exists that LC and DDC, as well as peripheral blood dendritic cells and monocytes from atopic individuals, can bind monomeric IgE via the high-affinity receptor for IgE (Fc epsilonRI). We have now found that Fc epsilonRI, both quantitatively and qualitatively, is the pivotal serum IgE-binding structure on APC of atopic individuals, that Fc epsilonRI on APC functions as allergen-focusing molecule and that allergens are more efficiently taken up, processed and presented to T cells following targeting to APC via Fc epsilonRI compared to allergen binding to APC in the conventional manner. In vivo, Fc epsilonRI-IgE-dependent allergen presentation may critically lower atopic individuals' threshold to mount allergen-specific T cell responses. This would result in the perpetuation of allergen-specific IgE production (type I reactions) and perhaps even in the occurrence of T-cell-mediated delayed-type hypersensitivity reactions in allergen-exposed tissues.