A dynamic immunological synapse mediates homeostatic TCR‐dependent and ‐independent signaling

For homeostasis, T cells integrate non-cognate TCR-dependent and -independent signals to survive and weakly proliferate. In contrast to antigen-specific, stable, and long-lived contacts, signaling in short-lived homeostatic interactions depends upon the coordination of ongoing T-cell migration on the surface of DC and signaling at the cell-cell junction. To mimic peripheral tissues and analyze how T-cell migration and cell-cell signaling are integrated, we used live-cell imaging and 3-D reconstruction of fixed conjugates between DO11.10 T cells and DC in 3-D low-density collagen matrices. T cells simultaneously maintained amoeboid migration and polarized towards the DC, leading to a fully dynamic interaction plane that delivered signals for homeostatic T-cell survival and proliferation. The contact plane comprised three zones, the actin-rich leading edge poor in signal but driving migration, a mid-zone mediating TCR/MHC-induced signal associated with proliferation, and the rear uropod mediating predominantly MHC-independent signals. Thus a dynamic immunological synapse with distinct signaling sectors enables moving T cells to serially sample resident tissue cells and acquire molecular information "en passant".