Body barrier surveillance by epidermal gammadelta TCR

The surveillance of body barriers relies on resident T cells whose repertoires are biased toward particular γδ T cell receptor lineages according to location. These γδ TCRs were shown to recognize stress-emergent ligands. Using intravital dynamics-immunosignal correlative microscopy, we report that epidermal T cell-expressed Vγ5 TCRs were constitutively clustered and functionally activated in vivo at steady-state, forming bona-fide immunological synapses that polarized and anchored T cell projections at squamous keratinocyte tight junctions. This synaptogenesis depended on TCR variable domains, Lck and αE(CD103)β7-integrin, but not the γδ lineage or NKG2D. In response to tissue stress, TCR-proximal signals did not increase significantly but underwent stress mode-dependent re-localization. Thus, the γδ TCR orchestrates barrier surveillance pro-actively, presumably by recognizing steady-state-expressed tissue ligands.