Endocytosis Mutants: Antigen Processing

内吞作用在许多过程中起着重要作用， 包括营养摄取、生长因子作用、抗原 呈现和维持质膜组成。 体细胞遗传学已经成功地用于分析 复杂内吞系统的一部分。 为了刺激 T淋巴细胞，大多数蛋白抗原必须裂解成肽 结构域并在抗原呈递结构域的表面上表达， 与主要产品相关的细胞 组织相容性复合体（MHC）。 提供资料说明 参与抗原呈递的特异性酶， 组织蛋白酶缺陷的抗原呈递细胞系 B是一种内切蛋白酶，将通过流式分选分离。 的 这些突变体将抗原呈递给T细胞的能力将是 测定 假定的突变体将有助于探索 抗原呈递机制，在重建内吞 在体外处理，并在分析的途径， 水解酶被递送到内吞隔室。 来自细胞外环境的物质的内化 内吞作用（endocytosis）是基本的细胞功能。 中 依赖于内吞作用的重要生理过程是 免疫原性外来物质的加工和呈递 （抗原）通过某些细胞类型（抗原呈递细胞）， 免疫系统的其他细胞。 拟议的研究将 提高我们对外来抗原如何被加工的理解 在抗原呈递细胞中。 这些知识将是重要的 不仅从免疫反应的角度来看， 因为它将提供进一步的洞察力， 细胞外物质通过内吞作用进入细胞。

Endocytosis plays a fundamental role in a number of processes, including nutrient uptake, growth factor action, antigen presentation and maintenance of plasma membrane composition. Somatic cell genetics has been successfully used to analyze protions of the complex endocytic system. In order to stimulate T lymphocytes, most protein antigens must be cleaved into peptide domains and expressed on the surface of an antigen-presenting cell in association with the products of the major histocompatibility complex (MHC). To provide information about the specific enzymes involved in antigen presentation, mutants of an antigen-presenting cell line which are defective in cathepsin B, an endoprotease, will be isolated by flow sorting. The ability of these mutants to present antigen to T cells will be determined. The putative mutants will be useful in exploring the mechanism of antigen presentation, in reconstituting endocytic processing in vitro, and in analyzing the pathways by which hydrolytic enzymes are delivered to endocytic compartments. Internalization of materials from the extracellular environment (endocytosis) is a fundamental cellular function. Among the important physiological processes that depend upon endocytosis is the processing and presentation of immunogenic foreign substances (antigens) by certain cell types (antigen-presenting cells) to other cells of the immune system. The proposed research will enhance our understanding of how foreign antigens are processed in antigen presenting cells. This knowledge will be important not only from the point of view of the immune response, but also because it will provide further insight into the fate of extracellular materials taken into cells by endocytosis.