CD1-lipid reactivity of epidermal T cells

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DESCRIPTION (provided by applicant): Since the initial discovery of γδ cells 30 years ago, non-classical MHC molecules have been proposed as antigens or antigen presenting molecules for these cells. In the intervening years, individual T cell clones have been identified with reactivity to CD1 and TL molecules but MHC reactivity has not been shown for populations of γδ cells. Recent data from two groups has now shown that the Vδ1+ TCR from human peripheral blood and intestinal γδ cells can directly bind to CD1d-αGalCer and CD1d-sulfatide. Interestingly, the Vδ1+ TCR is also used by epidermal-resident γδ cells in both human and mouse skin. CD1 expression is upregulated on epidermal cells during skin inflammation and disease and the epidermis is a rich source of lipids and skin oils. This raises the possibility tha CD1-lipid reactivity may be characteristic of all Vδ1+ T cells, including those that are resident i the epidermis. We propose to test the hypothesis that CD1-skin lipid antigens can provide a stress-signal of damage or disease in the epidermis to neighboring Vδ1+ T cells to activate their wound healing functions. We will test this hypothesis by determining if the human or mouse Vδ1+ TCR can interact with CD1-lipid antigens and by investigating whether CD1d expression during wound healing impacts epidermal γδ cell wound healing responses. If found to be a prototypic stress-signal for γδ cell activation, CD1 or skin lipids may then be considered as targets in future strategies to improve healing of chronic wounds as well as other skin inflammatory or autoimmune diseases.