T- and B-cell interaction: 2 signals for IgE production. IgM-facilitated uptake of allergen (Ag) by an antigen-specific T-cell is followed by processing (1) and presentation in the context of MHC class II molecules. Recognition of this complex by the T-cell receptor (TCR) of the responding Th2 cell induces (2) CD40L expression. CD40L-induced aggregation of CD40 then triggers expression (3) of B7 (CD80). Subsequent interaction of B7 with CD28 on the surface of the T cell delivers a costimulatory signal (4) that amplifies cytokine synthesis (5) and the T cell–proliferative response. IL-4 produced in response to the synergistic TCR and CD28 signals binds to IL-4R (signal 1), which, in conjunction with CD40 ligation (signal 2), triggers the IgE isotype switch, B-cell proliferation, and expansion of the IgE-producing clone.