Thy-1+ dendritic epidermal T cells (DETC) express an invariant gammadelta T cell receptor (TCR) and are only found in the skin. This population has been well characterized and represents the prototype invariant gammadelta T cell. DETC recognize and respond to self antigens expressed by neighboring keratinocytes after damage or disease. Once keratinocyte distress is detected, the DETC respond by the local secretion of KGF, an epithelial specific growth factor, and the production of chemokines which may direct other cell types to sites of damage in the epithelium. These results indicate a novel role for epithelial gammadelta T cells in recognition and repair of epithelial cells damaged by disease or insult. Identification of the antigen for the DETC is an important and necessary step in understanding the newly defined physiological role played by these cells. Identification of the antigen for the DETC is an important and necessary step in understanding the newly defined physiological role played by these cells. The goal of this project is to identify the antigen for the DETC and properties of antigen recognition in the following aims: (1) Identification of the DETC antigen. We have obtained highly-purified stimulatory material from keratinocytes and established that it is non-peptidic in nature. Ongoing analysis will provide complete identify. (2) Characterization of DETC antigen binding to TCR. Soluble Vgamma3Vdelta1 TCR molecules are being produced to examined antigen binding properties and structural features. (3) Dissection of the requirement for an antigen present molecule. We will isolate and characterize molecules that interact with antigen that may represent putative presenting molecules. Information gained in understanding antigens and properties of antigen recognition of the DETC may be applicable to populations of gammadelta T cells resident in other epithelial tissues. Once established, a paradigm for epithelial gammadelta T cell specificity will be useful for manipulation of the presence of these cells in epithelial diseases such as asthma, inflammatory bowel disease, psoriasis and wound healing.