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

Ⅰ类MHC皮肤抗原作为DETC Delta/GAMA TCR的识别靶标

• 批准号: 3728172
• 负责人: IWONA STROYNOWSKIN
• 金额: --
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3728172
• 关键词: MHC class I antigen; T cell receptor; antigen presentation; cytokine; dendritic cells; enzyme linked immunosorbent assay; flow cytometry; molecular cloning; receptor binding; receptor expression; skin; stress proteins

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.

具体目的：研究树突的分子机制