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

具体目标：树突状细胞的分子机制 表皮T细胞（DETC）在皮肤的正常免疫监视过程中， 不太了解。虽然导致DETC激活的条件 已经部分表征，特异性配体被 这些细胞的γ δ受体仍然未知。最近的研究表明 DETC的γ δ TCR和一些非经典I类MHC抗原， 在表皮的邻近细胞中表达。这两种分子都是 参与消除受感染或“应激”细胞。Thr 拟议的研究将测试的假设，非经典类I MHC蛋白质，Qa-2，与皮肤表达的肽抗原复合， 作为DETC的γ δ TCR的识别靶标。 1)为了鉴定哪些皮肤细胞表达Qa-2，组织培养表皮细胞 用Qa-2特异性抗体对细胞系和克隆进行分型。 在用细胞因子刺激后监测Qa水平的诱导 以及在热休克或化学应激的细胞中。 2)将检查Qa-2转染的皮肤细胞的能力， 触发DETC激活。细胞因子、病原体和应激对 将测试Qa-2的识别（DETC的刺激）。 3)病原体衍生的、皮肤表达的肽抗原，其能够结合 如果Qa-2在以下情况下刺激DETC，将对其进行鉴定和检测： Qa-2分子。

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.