Body-barrier surveillance by epidermal γδ TCRs.
The surveillance of body barriers relies on resident T cells whose repertoires are biased toward particular γδ T cell antigen receptors (TCRs) according to location. These γδ TCRs can recognize ligands that emerge after stress. Through the use of intravital dynamics-immunosignal correlative microscopy, we found that γ-chain variable region 5 (V(γ)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 α(E)β(7) but not the γδ 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 γδ TCR orchestrates barrier surveillance proactively, presumably by recognizing tissue ligands expressed in the steady state.
Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Grzegorz
G
Chodaczek
Veena
V
Papanna
M Anna
MA
Zal
Tomasz
T
Zal
D000818:Animals; D004817:Epidermis / Q000276:immunology*; D015603:Keratinocytes / Q000276:immunology; D008024:Ligands; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism; D051379:Mice; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology
D008024:Ligands; D016692:Receptors, Antigen, T-Cell, gamma-delta; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)