CLASS I MHC SKIN ANTIGEN AS RECOGNITION TARGET FOR DELTA/GAMA TCR OF DETC

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Specific Aims: The molecular mechanisms employed by the dendritic epidermal T cells (DETC) during normal immunosurveillance of the skin are poorly understood. While the conditions leading to the DETC activation have been partially characterized, the specific ligand(s) recognized by gammadelta receptors of these cells remain unknown. Recent studies suggest that gammadelta TCR of DETC and some nonclassical class I MHC antigens are expressed in neighboring cells of epidermis. Both types of molecules were implicated in the elimination of infected or "stressed" cells. Thr proposed research will test the hypothesis that the nonclassical class I MHC protein, Qa-2, complexed with skin-expressed peptide-antigens, serves as a recognition target for gammadelta TCR of DETC. 1) To identify which skin cells express Qa-2, the tissue-culture epidermal cell lines and clones will be typed with Qa-2 specific antibodies. Induciton of Qa levels will be monitored after stimulation with cytokines as well as in the heat-shocked or chemically-stressed cells. 2) The Qa-2-transfected skin cells will be examined for their capacity to trigger DETC activation. The effects of cytokines, pathogens and stress on recognition of Qa-2 (stimulation of DETC) will be tested. 3) Pathogen-derived, skin-expressed peptide antigens capable of binding to Qa-2 will be identified and tested if they stimulate DETC in the context of Qa-2 molecules.