TCR triggering on the move: diversity of T-cell interactions with antigen-presenting cells

Polarized T cells are mobile cells optimized for migration, receptor scanning, and signaling. When in contact with antigen-presenting cells (APCs), polarized T cells can develop a spectrum of biophysical interaction modes ranging from adhesive sticking to dynamic crawling. Both static and dynamic contacts support sustained triggering of the T-cell receptor (TCR), leading to signal induction, T blast formation, and proliferation. In dynamic interactions, T cells crawl across the surface of the APC at speeds of 2-6 micro m/min and simultaneously establish an asymmetric tight yet mobile junction plane, representing a dynamic immunological synapse. In dynamic synapses three functional compartments of the polarized T cell are in close contact with the APC surface, i.e. leading edge, cell body and uropod. Through its mobility, the asymmetric junction is topographically suited for receptor scanning and engagement at the leading edge, retrograde receptor movement along the junction, and exit from the uropod. Herein we develop a model on scanning encounters between T cells and APCs that includes the simultaneous engagement of T-cell leading edge and uropod and implicates a serial receptor triggering mode in cell-cell recognition.