Body-barrier surveillance by epidermal γδ TCRs

The surveillance of body barriers relies on resident T cells whose repertoires are biased toward particular gamma delta T cell antigen receptors (TCRs) according to location. These gamma delta TCRs can recognize ligands that emerge after stress. Through the use of intravital dynamics-immunosignal correlative microscopy, we found that gamma-chain variable region 5 (V(gamma)5) TCRs expressed by epidermal T cells were constitutively clustered and functionally activated in vivo at steady state, forming true immunological synapses that polarized and anchored T cell projections at squamous keratinocyte tight junctions. This synaptogenesis depended on TCR variable domains, the kinase Lck and the integrin alpha(E)beta(7) but not the gamma delta lineage or the receptor NKG2D. In response to tissue stress, TCR-proximal signals did not increase substantially but underwent stress mode-dependent relocalization toward the basal epidermis and Langerhans cells. Thus, the gamma delta TCR orchestrates barrier surveillance proactively, presumably by recognizing tissue ligands expressed in the steady state.