Different T Cell Receptor Signals Determine CD8+ Memory Versus Effector Development

Following infection, naive CD8(+) T cells bearing pathogen- specific T cell receptors ( TCRs) differentiate into a mixed population of short- lived effector and long- lived memory T cells to mediate an adaptive immune response. How the TCR regulates memory T cell development has remained elusive. Using a mutant TCR transgenic model, we found that point mutations in the TCR beta transmembrane domain (beta TMD) impair the development and function of CD8(+) memory T cells without affecting primary effector T cell responses. Mutant T cells are deficient in polarizing the TCR and in organizing the nuclear factor kappa B signal at the immunological synapse. Thus, effector and memory states of CD8(+) T cells are separable fates, determined by differential TCR signaling.