Distinct intracellular compartments involved in invariant chain degradation and antigenic peptide loading of major histocompatibility complex (MHC) class II molecules.
Distinct intracellular compartments involved in invariant chain degradation and antigenic peptide loading of major histocompatibility complex (MHC) class II molecules.
复制标题
DOI：
10.1083/jcb.139.6.1433
复制
发表时间：
1997-12-15
期刊：
影响因子：
--
通讯作者：
Pieters J
中科院分区：
文献类型：
--
作者：
Ferrari G;Knight AM;Watts C;Pieters J
主要组织相容性复合体(MHC)II类分子通过与不变链(II)的瞬时结合被运送到细胞内的MHC II类隔室。去除不变链后，多肽可以被负载到II类分子上，这一过程是由人类白细胞抗原-DM(人类白细胞抗原-DM)分子催化的。这里我们展示了MHC II类隔室由两个物理上和功能上不同的细胞器组成。新合成的MHC II/II类复合体是针对缺乏人类白细胞抗原-DM分子的胞内细胞器，在那里发生II降解。从这些细胞器中，II类分子被运输到一个独特的含有人类白细胞抗原-DM的细胞器，在那里多肽被加载到II类分子上。后一种细胞器不能通过液体相内吞作用直接进入，这表明它不是内体途径的一部分。然而，通过抗原特异的膜免疫球蛋白摄取导致在人类白细胞抗原-糖尿病阳性细胞器中有少量的抗原。第二类-多肽复合体从这个多肽负载室转运到质膜，部分经过内吞细胞器转运。存在两个独立的隔室，一个参与II类分子的去除，另一个负责装载类II类分子的依赖于HLA-DM的多肽，这可能通过选择性地将多肽受体II类分子和人类白细胞抗原-DM募集到相同的亚细胞位置来提高抗原提呈的效率。
Major histocompatibility complex (MHC) class II molecules are transported to intracellular MHC class II compartments via a transient association with the invariant chain (Ii). After removal of the invariant chain, peptides can be loaded onto class II molecules, a process catalyzed by human leukocyte antigen-DM (HLA-DM) molecules. Here we show that MHC class II compartments consist of two physically and functionally distinct organelles. Newly synthesized MHC class II/Ii complexes were targeted to endocytic organelles lacking HLA-DM molecules, where Ii degradation occurred. From these organelles, class II molecules were transported to a distinct organelle containing HLA-DM, in which peptides were loaded onto class II molecules. This latter organelle was not directly accessible via fluid phase endocytosis, suggesting that it is not part of the endosomal pathway. Uptake via antigen-specific membrane immunoglobulin resulted however in small amounts of antigen in the HLA-DM positive organelles. From this peptide-loading compartment, class II–peptide complexes were transported to the plasma membrane, in part after transit through endocytic organelles. The existence of two separate compartments, one involved in Ii removal and the other functioning in HLA-DM–dependent peptide loading of class II molecules, may contribute to the efficiency of antigen presentation by the selective recruitment of peptide-receptive MHC class II molecules and HLA-DM to the same subcellular location.