Antigen-induced regulatory T cells: cellular basis of the antigen specificity. (A) Antigen specificity is ensured at 3 stages: presentation, activation, and recognition. (i) Presentation. A dendritic cell (DC) is presented to a conventional T cell (T) combined with a regulatory signal provided by, or accompanying the DC. The regulatory signal induces differentiation of the antigen-specific conventional T cell into an antigen-specific regulatory T cell (Tr). (ii) Activation. The Tr must encounter the same antigen again in order to become activated and fully competent to suppress the specific immune response. This antigen-driven activation ensures that suppression is limited to a particular target. (iii) Recognition. Two mechanisms support the antigen-specificity target cell (APC or T cell) recognition by Trs. First, some Trs specifically recognize MHC class I antigens on allogeneic APCs. The second mechanism is illustrated in Figure 2B. (B) Antigen-specific recognition of CD8 effector T cells by regulatory T cells. This mechanism has been described in a murine model of skin allotransplantation.30 The Trs acquire allogeneic MHC class I molecules from APCs and express them on their surface. This transfer allows the Trs to recognize autologous cytotoxic CD8 effector T cells bearing a TCR specific for the transferred MHC class I molecule.
