Naïve T lymphocytes sense foreign antigens by establishing contacts with dendritic cells (DCs). At the immunological synapse between the T cell and a DC, T cell receptors (TCRs) are serially engaged and triggered by specific ligands. The amount and duration of TCR triggering and the efficiency of signal amplification determine T cell commitment to proliferation and differentiation. The nature and availability of DCs bearing antigen and costimulatory molecules shape the T cell response, giving rise to distinct functional outputs such as effector and memory T cell generation or T cell tolerance.