Visualizing the rapid and localized keratinocyte expression of dendritic epidermal T cell antigens in response to wounding (93.3)

Abstract

Abstract Within the skin, dendritic epidermal T cells (DETC) function at the interface of innate and adaptive immunity, playing important roles in homeostasis, tumor surveillance and wound repair. Central to their role in wound repair is stimulation of DETC through their monoclonal Vγ3Vδ1 T cell receptor (TCR) by an uncharacterized antigen expressed on stressed keratinocytes. While only DETC proximal to the wound site become activated, expression patterns and kinetics of antigens that stimulate DETC activation are uncharacterized. Using soluble DETC TCR tetramers, we show that the DETC TCR binds to a glycosylated, cell surface expressed, protein that is constitutively expressed by transformed epithelial cell lines in vitro. Additionally, in situ studies show that DETC TCR ligands are rapidly upregulated by keratinocytes proximal, but not distal to, wound edges. Following antigen expression, DETC become activated and antigen expression is subsequently down-modulated. Furthermore, inhibition of TCR-ligand interactions using DETC TCR tetramers delays wound repair in vivo, highlighting the importance of rapid, TCR mediated, DETC activation by keratinocytes for proper wound healing. This study represents the first visualization of DETC TCR ligand expression by keratinocytes in murine skin and provides a mechanism for the rapid and localized activation of DETC in response to wounding. Supported by the National Institutes of Health (AI064811 to W.L.H, A142267 to L.T.), and the National Science Foundation Graduate Research Fellowship to H.K.K.