PEPTIDE LOADING ONTO CLASS I MHC MOLECULES

主要组织相容性复合体(MHC)分子负责 抗原被提呈给T细胞。最近的观察表明 I类MHC分子呈现来自内源性的多肽 蛋白质，而II类MHC分子提供源自 通过内吞作用进入细胞的蛋白质。这种二分法表明 这两种类型的MHC分子通过分离和 不同的过程。I类分子最有可能在 细胞的胞吐隔间。因为多肽可能来源于 定位于细胞核、细胞质、线粒体和线粒体的蛋白质 细胞内有多种膜性结构，显然有许多 多肽必须穿过膜才能到达I类分子。它 似乎特定的蛋白质可能介导了多肽的转移 到I类分子上。第I类分子的组装是 受多肽的影响，但多肽效应的确切性质是 未知。同样，精确的亚细胞位置组装和 多肽加成的发生仍然是个谜。 将通过以下方式研究组装和多肽加载过程 生物合成和形态技术。亚细胞分馏 将进行分析以进一步检查亚细胞 负责生成和组装第I类多肽的细胞器 分子。多肽加载过程中独有的蛋白质，参与 引导I类分子通过相关的细胞内隔室 将被识别和刻画。 拟议的研究应该阐明多肽是如何产生的，以及 被I类分子获得。这些信息将是无价的 设计新的疫苗，应该有助于我们理解 为什么自我分子可能会引起自身免疫反应。

The major histocompatibility complex (MHC) molecules are responsible for the presentation of antigen to T cells. Recent observations indicate that class I MHC molecules present peptides derived from endogenous proteins while class II MHC molecules present peptides derived from proteins imported into the cell by endocytosis. This dichotomy suggests that the two types of MHC molecules acquire peptides by separate and distinct processes. The class I molecules most likely obtain peptides in the exocytotic compartment of the cell. As peptides may originate from proteins localized in the nucleus, the cytoplasm, mitochondria and a variety of membranous structures in the cell, it is apparent that many peptides have to cross a membrane to reach the class I molecules. It seems likely that specific proteins may mediate the transfer of peptides onto class I molecules. The assembly of the class I molecules is influenced by peptides but the exact nature of the peptide effect is unknown. Likewise, the precise subcellular site where assembly and peptide addition occurs remains enigmatic. The assembly and peptide-loading processes will be studied by biosynthetic and morphological techniques. Subcellular fractionation analyses will be carried out to further examine the subcellular organelles responsible for the peptide generation and assembly of class I molecules. Proteins unique to the peptideloading process and engaged in guiding class I molecules through the relevant intracellular compartments will be identified and characterized. The proposed studies should shed light on how peptides are generated and acquired by class I molecules. Such information will be invaluable in designing novel vaccines and should contribute to our understanding of why self-molecules might give rise to auto-immune reactions.