W e show in these studies that Qa-1–dependent CD8⁺ T cells are involved in the establishment and maintenance of peripheral self tolerance as well as facilitating affinity maturation of CD4⁺ T cells responding to foreign antigen. We provide experimental evidence that the strategy used by the Qa-1–dependent CD8⁺ T cells to accomplish both these tasks in vivo is to selectively downregulate T cell clones that respond to both self and foreign antigens with intermediate, not high or low, affinity/avidity. Thus, the immune system evolved to regulate peripheral immunity using a unified mechanism that efficiently and effectively permits the system to safeguard peripheral self tolerance yet promote the capacity to deal with foreign invaders.