T cell responses to antigen: hasty proposals resolved through long engagements

T cells discriminate between peptide-MHC complexes on the surfaces of antigen presenting cells to enact appropriate downstream responses. Great progress has been made over the last 15 years in understanding varied aspects of T cell activation on short timescales (minutes), yet the mechanics and significance of long term T cell receptor signaling (hours or days) remain unclear. Furthermore, there remain some controversies regarding the correlation of the biophysical parameters of ligand-receptor interactions with the scaling of downstream effector functions. Here we review recent studies that emphasize the importance of long-term engagement of antigens to fine-tuning the activation of T cells over the duration of the complete immune response. We discuss how T cells dynamically regulate T cell receptor signaling via antigen crosstalk, competition and consumption to accurately counter antigenic challenges.