We 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.
Hong Jiang, Yilun Wu, Bitao Liang, Zongyu Zheng, Guomei Tang, Jean Kanellopoulos, Mark Soloski, Robert Winchester, Itamar Goldstein, Leonard Chess
Summary of HEL-specific CD4+ T cell clones tested in the CFSE assay