4.2 Role of IgE in enhancing T cell responses.
The concept of IgE-facilitated allergen presentation was first elucidated in studies that showed that complexes of specific IgE with allergens could significantly enhance the responses of allergen-specific T cells at low allergen concentrations16,19,67. This IgE mediated allergen presentation, or facilitated allergen presentation, involved binding the IgE-allergen complexes to CD23 on antigen-presenting B cells (Figure 2).
Around the same time, it became apparent that dendritic cells and monocytes from peripheral blood express the high-affinity IgE receptor (FcεRI) and could also activate allergen-specific T cells in an IgE-facilitated manner17,52
These findings are relevant because allergen levels in the respiratory tract are extremely low upon natural allergen exposure. The IgE-facilitated presentation of allergens to T cells enables T cell activation at these low allergen exposures.
The binding of allergen-IgE complexes to antigen-presenting cells is dependent on several parameters. In principle and in a model system, monoclonal IgE is sufficient to present allergen68. Furthermore, the complexity of IgE binding to multiple epitopes on allergens and their affinity has been shown to correlate with the facilitation of T cell responses69. These findings suggest that the number of IgE molecules bound per allergen may play an essential role in this complex formation and binding. This was confirmed recently in a study by Villazala-Merino et al.70 where non-FcεRI cross-linking monoclonal IgE-monomeric allergen complexes, i.e. (one IgE molecule binding two Bet v1 molecules) could enhance T cell activation. However, this activation was further enhanced by 100-fold when cross-linking IgE-allergen oligomer complexes were used (multimeric complexes). Finally, the heterogeneity of allergen epitopes recognized by IgE, the presence of competing IgG(4) antibodies, the density of CD23 on the surface of B cells in peripheral blood of allergic patients correlates with the ability to enhance T cell activation by allergen-IgE complexes 71.