Adaptive immunity requires that T cells efficiently scan diverse cell surfaces in order to identify cognate antigen. However, the basic cellular mechanisms remain unclear. Here we investigated this process using vascular endothelial cells, antigen presenting (APC) cells that possess a unique and extremely advantageous, planar morphology. High-resolution imaging revealed that CD4 memory/effector T cells dynamically probe the endothelium by extending sub-micron-scale, actin-rich ‘invadosome/podosome-like protrusions’ (ILPs). The intimate intercellular contacts enforced by ILPs consistently preceded, and supported T cell activation in response to endothelial MHC-II/antigen. The resulting calcium flux stabilized dense arrays of ILPs (each enriched in TCR, PKC-θ, ZAP-70, phosphotyrosine and HS1), forming what we term a ‘podo-synapse’. Similar findings were made using CD8 cytotoxic T lymphocytes on endothelium. Furthermore, careful reexamination of both traditional APC models and professional APCs suggests broad relevance for ILPs in facilitating antigen recognition. Together, our results indicate that ILPs function as sensory organelles that serve as actuators of immune surveillance.

Endothelial and epithelial barrier disruptions are detected via local decrease in cellular tension, which are coupled to reactive oxygen species–dependent self-restorative actin remodeling dynamics.

Our improving understanding of monocyte trafficking and migration mechanisms has begun to shed light on the functions of these often enigmatic cells. Continued progress in this area will be critical for elucidating roles of monocytes in disease and for developing therapeutics that target monocytes.

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