EXTENSIVE TRAFFICKING OF MHC CLASS II-INVARIANT CHAIN COMPLEXES IN THE ENDOCYTIC PATHWAY AND APPEARANCE OF PEPTIDE-LOADED CLASS-II IN MULTIPLE COMPARTMENTS
EXTENSIVE TRAFFICKING OF MHC CLASS II-INVARIANT CHAIN COMPLEXES IN THE ENDOCYTIC PATHWAY AND APPEARANCE OF PEPTIDE-LOADED CLASS-II IN MULTIPLE COMPARTMENTS
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DOI：
10.1016/1074-7613(95)90080-2
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发表时间：
1995-01-01
期刊：
影响因子：
32.4
通讯作者：
GERMAIN, RN
中科院分区：
文献类型：
--
作者：
CASTELLINO, F;GERMAIN, RN
主要组织相容性复合物II类分子结合并呈递进入内吞途径的蛋白抗原的T细胞片段。使用正常的B淋巴母细胞，我们结合了代谢脉冲追踪标记，高分辨率的细胞器分馏，和免疫沉淀检查II类贩运和抗原装载在生理模型系统。大多数新合成的II类不变链复合物首先进入早期内体，然后进入多个离散的内吞亚室与晚期内体和未成熟的溶酶体共分馏。不变链被删除，肽加载II类分子出现在这些后者不同的细胞器中。这些研究结果表明，II类分子的交通通过大部分的内吞途径，允许捕获不同的决定因素，在不同的pH值和蛋白水解活性的条件下提供。
Major histocompatibility complex class II molecules bind and present to T cells fragments of protein antigens entering the endocytic pathway. Using normal B lymphoblasts, we have combined metabolic pulse-chase labeling, high resolution organelle fractionation, and immunoprecipitation to examine class II trafficking and antigen loading in a physiological model system. Most newly synthesized class II-invariant chain complexes first entered early endosomes, then accessed multiple discrete endocytic subcompartments cofractionating with late endosomes and immature lysosomes. Invariant chain was removed and peptide-loaded class II molecules appeared in each of these latter distinct organelles. These findings suggest that class II molecules traffic through much of the endocytic pathway, permitting capture of distinct determinants made available under differing conditions of pH and proteolytic activity.