Lowering TCR expression on naive CD8+ T cells does not affect memory T-cell differentiation.

The generation of long-lived memory T (Tm) cells is critical for the success of vaccination, but the factors controlling their differentiation are still poorly defined. We examined the hypothesis that the level of T-cell receptor (TCR) engagement contributed to memory CD8(+) T-cell generation. By manipulating TCR expression levels on murine, naive ovalbumin (OVA)-specific CD8(+) T cells, we showed that the expansion of antigen (Ag)-specific CD8(+) T cells is minimally affected by the level of TCR expression. Indeed, naive CD8(+) T cells expressing as little as a 1000 TCRs (30-fold less) show only a 2.5-fold reduction in the number of effectors generated. Furthermore, the TCR expression levels influenced neither the acquisition of effector functions nor the generation of functional Tm cells. Our data indicate that during an in vivo immune response, a threshold in the number of TCRs engaged by naive CD8(+) T cells is required for full T-cell expansion but not for their differentiation into effector and Tm cells.