Figure 1

Thymic vaccination versus conventional vaccines. A. Conventional vaccines act on the mature peripheral lymphoid pool, in particular expanding existing T cells directed against the immunogen (blue square) derived from the disease-causing agent. Following subsequent infection, the T cell recognizes the pathogen, proliferates, mediates effector function and cytokines leading to immune response and elimination of the disease. For simplicity, the B lymphocyte response is not shown. B. Thymic vaccination offers a way to alter the primary T cell repertoire through exposure of immature thymocytes to APL with reduced TCR affinity relative to cognate antigens recognizing those TCRs. Thymocyte maturation (i.e. positive selection) is enhanced by the low affinity interaction between a TCR and an MHC-bound APL (green ribbon) in the thymus, with subsequent emigration of mature cells into the peripheral T lymphocyte pool. Those peripheral T cells can respond to cognate antigen (red triangle). Thus, variants of cognate antigens derived from infectious agents, tumors, etc. could be employed for peptide-driven maturation of thymocytes bearing pathogen-specific TCRs.