EMPTY CLASS II MHC ON DENDRITIC CELLS AND MICROGILIA

描述（研究者摘要）：研究的广泛、长期目的 拟议的研究是表征生物化学过程， 一种新抗原加工和装载途径的免疫学意义 最近显示利用空的或“肽接受”的细胞表面MHC类 某些专职抗原细胞中的II蛋白。拟议的研究是 目的是确定MHC II类稳定性与 空分子在树突状细胞表面的表达，以研究 空的II类MHC分子的表达和功能能力， 中枢神经系统小胶质细胞，以鉴定参与 未成熟树突状细胞的细胞外抗原加工，并评估 细胞外与细胞内抗原加载途径的重要性 在树突细胞和小胶质细胞中。这些目标将通过 空的和装载肽的MHC分子的生物化学表征， 抗体和肽结合测定、纯化和表征 分泌的蛋白酶活性，以及细胞内蛋白酶的特异性抑制剂的用途， 和细胞外加工途径。这项研究是一项 互动研究项目组。IRPG的总体目标是 表征抗原加工和呈递的新途径， 细胞外蛋白酶和空的II类MHC蛋白， 最初在未成熟的树突细胞中发现。该项目支持， 通过关注抗原加工和肽的生物化学方面， 负载在树突细胞和小胶质细胞中。同伴项目的重点是MHC 运输和抗原呈递。

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.