TCR-ligand interactions are required for murine epidermal Vγ3Vδ1 T cell development

Abstract

Abstract Dendritic epidermal T cells (DETC), which bear the Vγ3Vδ1 T cell receptor (TCR), are the exclusive T cell population resident in the murine epidermis where they act as sentinels for neighboring keratinocytes. γδ T cells differentiate from lymphoid precursors largely within the thymic microenvironment in a highly organized manner. Cellular selection processes are also believed to be involved and indeed several lines of evidence suggest that proper development and homing of the Vγ3Vδ1+ subset does require positive selection events in the fetal thymus. To evaluate the role of TCR interactions with cognate ligand in Vγ3Vδ1 T cell development and maturation, we used a soluble DETC TCR tetramer to characterize ligand expression in the fetal thymus and skin. We show that temporal expression of ligand in the thymus closely mimics the window of DETC intrathymic development. Ligand expression is independent of Skint1, a molecule shown to be important for thymic maturation of DETC and their subsequent residence in the epidermis. Furthermore, using the soluble DETC TCR tetramer as a ligand blocking reagent, we show that in fetal thymic reaggregation cultures, TCR-ligand interactions are essential for DETC development and maturation. Current experiments are investigating the nature of the ligand-expressing thymic epithelial cell population. Understanding TCR-ligand interactions involved in DETC development may provide important insight into identifying the enigmatic DETC antigen.