EMPTY CLASS II MHC ON DENDRITIC CELLS AND MICROGILIA

说明(研究人员摘要)： 建议的研究是描述生物化学过程和 一种新的抗原加工和装载途径的免疫学意义 最近发现利用空的或“多肽受体”的细胞表面MHC类 某些专业抗原细胞中的II蛋白。拟议的研究是 旨在确定MHC II类稳定性和MHC II类之间的关系 树突状细胞表面空分子的表达 空的II类MHC分子在细胞上的表达和功能 中枢神经系统小胶质细胞中的蛋白水解酶(S)参与鉴定 未成熟树突状细胞胞外抗原的处理 细胞外与细胞内抗原装载途径的重要性 在树突状细胞和小胶质细胞中。这些目标将通过以下方式实现 空载和多肽MHC分子的生物化学表征 抗体和多肽结合分析、纯化和鉴定 分泌性蛋白水解酶活性，以及细胞内特异性抑制剂的使用 和细胞外处理途径。这项拟议的研究是 互动研究项目组。该小组的整体目标是 描述一种新的抗原处理和提呈途径，包括 胞外蛋白酶和空的II类MHC蛋白 最初在未成熟的树突状细胞中发现。本项目支持这一点 目标集中在抗原处理和多肽的生物化学方面 负载树突状细胞和小胶质细胞。配套项目的重点是MHC 贩卖和抗原呈递。

DESCRIPTION (investigator's abstract): The broad, long-term objective of the proposed research is to characterize the biochemical processes and immunological importance of a novel antigen processing and loading pathway recently shown to utilize empty or "peptide-receptive" cell-surface MHC class II proteins in certain professional antigen cells. The proposed research is intended to determine the relationship between MHC class II stability and expression of empty molecules on the surface of dendritic cells, to investigate the expression and functional capacity of empty class II MHC molecules on central nervous system microglia cells, to identify the protease(s) involved in extracellular antigen processing in immature dendritic cells, and to evaluate the importance of extracellular versus intracellular antigen loading pathways in dendritic cells and microglia. These goals will be achieved through biochemical characterization of empty and peptide-loaded MHC molecules using antibody and peptide binding assays, purification and characterization of secreted protease activity, and the use of specific inhibitors of intracellular and extracellular processing pathways. The proposed research is part of an interactive research project group. The overall objective of the IRPG is to characterize a novel pathway for antigen processing and presentation involving extracellular proteases and empty class II MHC proteins that has been identified initially in immature dendritic cells. This project supports that goal by focusing on biochemical aspects of antigen processing and peptide loading in dendritic cells and microglia. The companion project focuses on MHC trafficking and antigen presentation.