The space and time frames of T cell activation at the immunological synapse

The selective recognition of antigenic peptides by T cells requires the spatio/temporal integration of a panoply of molecular triggers. The space frame of T cell antigen receptors (TCR) interaction with peptide/MHC complexes (pMHC) displayed by antigen presenting cells is delineated by the micrometer-scale area of the immunological synapse. The time frame of T cell stimulation is governed by a series of short TCR–pMHC interactions that are integrated into sustained signaling leading to productive activation. We discuss here how approaching antigen recognition from the time and space angles is key to the comprehension of the puzzling process of T cell activation.