Allergen-specific IgE levels and ability of IgE-allergen complexes to cross-link determine extent of CD23-mediated T cell activation

Abstract Background CD23 mediates IgE-facilitated allergen presentation and subsequent allergen-specific T cell activation in allergic patients. Objective To investigate key factors regulating IgE-facilitated allergen presentation via CD23 and subsequent T cell activation. Methods To study T cell activation by free allergens and different types of IgE-Bet v 1 complexes we used a molecular model based on monoclonal human Bet v 1-specific IgE, monomeric and oligomeric Bet v 1 allergen, MHC-matched CD23-expressing B cell line and a T cell line expressing a human Bet v 1-specific T cell receptor. The ability to cross-link Fc epsilon (e) receptors of complexes consisting of either IgE and monomeric Bet v 1 or IgE and oligomeric Bet v 1 was studied in human FceRI-expressing basophils. T cell proliferation by monomeric or oligomeric Bet v 1 which cross-link Fc epsilon receptors to a different extent, was studied in allergic patients’ PBMCs with and without CD23-expressing B cells. Results In our model, non-crosslinking IgE-Bet v 1 monomer complexes as well as cross-linking IgE-Bet v 1 oligomer complexes induced T cell activation, which was dependent on the concentration of specific IgE. However, T cell activation by cross-linking IgE-Bet v 1 oligomer complexes was approximately 125-fold more efficient. Relevant T cell proliferation occurred in allergic patients’ PBMCs only in the presence of B cells and its magnitude depended on the ability of IgE-Bet v 1 complexes to cross-link CD23. Conclusion The extent of CD23-mediated T cell activation depends on the concentration of allergen-specific IgE and the cross-linking ability of IgE-allergen complexes.