FUNCTIONAL AND ULTRASTRUCTURAL EVIDENCE FOR INTRACELLULAR FORMATION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II-PEPTIDE COMPLEXES DURING ANTIGEN PROCESSING
FUNCTIONAL AND ULTRASTRUCTURAL EVIDENCE FOR INTRACELLULAR FORMATION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II-PEPTIDE COMPLEXES DURING ANTIGEN PROCESSING
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DOI：
10.1073/pnas.87.14.5553
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发表时间：
1990-07-01
影响因子：
11.1
通讯作者：
GEUZE, HJ
中科院分区：
文献类型：
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作者：
HARDING, CV;UNANUE, ER;GEUZE, HJ
抗原呈递需要天然抗原的细胞内加工以产生与主要组织相容性复合体II类（MHC-II）分子结合的免疫原性肽。在功能研究中，抗原处理引起的腹腔巨噬细胞，MHC-II-肽复合物在细胞内形成。未释放免疫原性肽以结合表面MHC-II分子。在这些巨噬细胞的冷冻切片中采用免疫金染色的超微结构研究显示，外周细胞质中的细胞内囊状空泡中存在大量MHC-II分子;其中大多数对lamp 1溶酶体/内体膜蛋白和组织蛋白酶D呈阴性。MHC-II分子也存在于含有组织蛋白酶D和land 1以及先前内化的金转铁蛋白的内体中。MHC-II分子的细胞内池仅略有减少，用放线菌酮治疗3小时，表明它主要由内吞，回收分子，而不是新生的。这些超微结构的研究支持的概念，有内吞作用的MHC-II分子进入内吞隔室，与我们早期的生化数据一致。此外，我们已经确定了不同的内吞隔室，必须介导抗原加工的重要功能，包括形成MHC-II肽复合物。
Antigen presentation requires intracellular processing of native antigens to produce immunogenic peptides that bind to major histocompatibility complex class II (MHC-II) molecules. In functional studies of antigen processing by elicited peritoneal macrophages, MHC-II-peptide complexes were formed intracellularly. Immunogenic peptides were not released to bind surface MHC-II molecules. Ultrastructural studies employing immunogold staining in ultrathin cryosections of these macrophages showed large amounts of MHC-II molecules in intracellular sac-like vacuoles in the peripheral cytoplasm; most of these were negative for the lamp 1 lysosomal/endosomal membrane protein and cathepsin D. MHC-II molecules were also present in endosomes containing cathepsin D and land 1 as well as previously internalized gold-transferrin. The intracellular pool of MHC-II molecules was only slightly decreased by treatment with cycloheximide for 3 hr, indicating that it consisted mainly of endocytosed, recycling molecules, as opposed to nascent ones. These ultrastructural studies support the notion that there is endocytosis of MHC-II molecules into endocytic compartments, consistent with our earlier biochemical data. Furthermore, we have defined the distinct endocytic compartments that must mediate important functions in antigen processing, including the formation of MHC-II peptide complexes.