PEPTIDE BINDING INHIBITS PROTEIN AGGREGATION OF INVARIANT-CHAIN FREE CLASS-II DIMERS AND PROMOTES SURFACE EXPRESSION OF OCCUPIED MOLECULES
PEPTIDE BINDING INHIBITS PROTEIN AGGREGATION OF INVARIANT-CHAIN FREE CLASS-II DIMERS AND PROMOTES SURFACE EXPRESSION OF OCCUPIED MOLECULES
复制标题
DOI：
10.1038/363725a0
复制
发表时间：
1993-06-24
期刊：
影响因子：
64.8
通讯作者：
RINKER, AG
中科院分区：
文献类型：
--
作者：
GERMAIN, RN;RINKER, AG
主要组织相容性复合体(MHC)I类分子从内质网(ER)的有效出口依赖于多肽结合1-7。对于MHC II类分子，不变链(II)促进新组装的无肽二聚体8-14的内质网退出。这就提出了一个问题，即在细胞的其他地方是否存在一种机制，决定了与多肽相关的第二类分子的选择性表达。我们在这里报道，在低pH和生理温度下，MHC II-II类复合体的解离导致蛋白质聚集体中包含空的II类，这种聚集被肽结合特异性地阻止。结合显示抗原暴露通过翻译后机制增加活细胞表面II类表达的数据12，这些结果为多肽依赖的细胞内编辑II类二聚体提供了证据，这限制了不适合抗原特异性T细胞激活的空分子的表面表达。
EFFICIENT egress of major histocompatibility complex (MHC) class I molecules from the endoplasmic reticulum (ER) depends on peptide binding1-7. For MHC class II molecules, invariant chain (Ii) promotes ER exit of newly assembled, peptide-free dimers8-14. This raises the question of whether a mechanism exists elsewhere in the cell that dictates selective expression of peptide-associated class II molecules. We report here that dissociation of MHC class II-Ii complexes at low pH and physiological temperature leads to inclusion of empty class II in protein aggregates, and that this aggregation is specifically prevented by peptide binding. Combined with data showing that antigen exposure increases cell surface class II expression on living cells by a post-translational mechanism12, these results provide evidence for peptide-dependent intracellular editing of class II dimers, which limits surface expression of empty molecules unsuitable for antigen-specific T-cell activation.