Sensitization is the process that converts a harmless antigen into an allergen. It begins when the antigen is taken up by dendritic cells in the airway or gut mucosa and presented on MHC class II to naive CD4+ T cells. In a person who will become allergic, the responding T cells differentiate toward the Th2 subset under the influence of epithelial-derived cytokines such as TSLP, IL-25, and IL-33, which are released when the mucosal barrier is disturbed. Th2 cells secrete IL-4 and IL-13, and these cytokines act on antigen-specific B cells during the same cognate interaction in which the B cell presents antigen to the T cell. IL-4 and IL-13, together with CD40–CD40L costimulation, activate the class-switch recombination machinery that replaces the B cell's IgM heavy-chain constant region with the IgE constant region. The B cell then secretes IgE specific for the original antigen.
IgE does not circulate free for long. It binds with very high affinity to FcεRI, the high-affinity IgE receptor, on the surface of tissue mast cells and blood basophils. Because the IgE is already bound, the mast cell is now armed: it carries antigen-specific receptors before it has ever encountered the antigen again. This is the decisive step. No symptoms occur during sensitization; the immune system has simply installed a loaded trigger. On a later exposure, antigen that reaches the tissue can bind and cross-link two or more adjacent IgE–FcεRI complexes, and that cross-linking is the signal that fires the cell.