Multiscale analysis of T cell activation: correlating in vitro and in vivo analysis of the immunological synapse

Recently implemented fluorescence imaging techniques, such as total internal reflection fluorescence microscopy and two-photon laser scanning microscopy, have made possible multiscale analysis of the immune response from single molecules in an interface to cells moving in lymphoid tissues and tumors. In this review, we consider components of T cell sensitivity: the immunological synapse, the coordination of migration, and antigen recognition in vivo. Potency, dose, and detection threshold for peptide-MHC determine T cell sensitivity. The immunological synapse incorporates T cell receptor microclusters that initiate and sustain signaling, and it also determines the positional stability of the T cells through symmetry and symmetry breaking. In vivo decisions by T cells on stopping or migration are based on antigen stop signals and environmental go signals that can sometimes prevent arrest of T cells altogether, and thus can change the outcome of antigen encounters.