Tonic T cell signalling and T cell tolerance as opposite effects of self-recognition on dendritic cells

Naive T cells spend most of their time scanning the surface of dendritic cells (DCs), indicating that self-MHC/T cell receptor (TCR) interactions between these immune cells occur routinely in peripheral organs during the steady state. Peripheral self-MHC recognition on DCs drives seemingly opposing effects in the absence of inflammatory stimuli such as deletion of certain self-reactive T cells as well as maintenance of the T cell responsiveness to antigen, both of which shape the T cell repertoire and regulate T cell responses. Here we review recent data on the role of self-MHC recognition on steady-state DCs in the periphery and propose that interactions between T cells and steady-state DCs display an analogy with selection processes that occur in the thymus: high affinity TCR/self-MHC interactions in the periphery result in T cell deletion, while low/intermediate affinity interactions result in tonic TCR signalling that is required to keep T cells responsive to antigen.