Assembly and transport properties of invariant chain trimers and HLA-DR-invariant chain complexes.
Assembly and transport properties of invariant chain trimers and HLA-DR-invariant chain complexes.
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DOI：
10.4049/jimmunol.148.11.3478
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发表时间：
1992-06
影响因子：
4.4
通讯作者：
C. Lamb;P. Cresswell
中科院分区：
文献类型：
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作者：
C. Lamb;P. Cresswell
MHC II类相关的不变链的行为作为一个居民的内质网蛋白在II类分子的情况下。在人类中，存在两种主要形式;一种是p35，与另一种p33的不同之处在于含有强内质网滞留信号的16个氨基酸的N-末端胞质延伸。在这里，我们表明，保留p33的一种机制是它与p35在混合不变链三聚体的协会。然而，即使对于p33同源三聚体，从内质网的转运也是低效的。在MHC II类阳性B细胞系中，不变链三聚体的形成是快速的，并且是九链α β不变链复合物组装中的第一中间体。随着时间的推移，逐渐形成三种更高分子量的复合物。这些分别对应于具有一个α β二聚体、两个α β二聚体和三个α β二聚体的不变链三聚体。在生物合成的早期没有检测到游离的α β二聚体。然而，从2小时的追逐开始，α β二聚体开始出现伴随着完全组装的α β不变链复合物的消失。该转化在4小时时几乎完全，并且推测反映了α β-不变链复合物的不变链组分的蛋白水解降解和能够结合抗原肽的内体α β二聚体的产生。
The MHC class II-associated invariant chain behaves as a resident endoplasmic reticulum protein in the absence of class II molecules. In humans, two predominant forms exist; one, p35, differs from the other, p33, by an N-terminal cytoplasmic extension of 16 amino acids that contains a strong endoplasmic reticulum-retention signal. Here we show that one mechanism for retention of p33 is its association with p35 in mixed invariant chain trimers. However, even for p33 homotrimers transport from the endoplasmic reticulum is inefficient. In an MHC class II-positive B cell line, the formation of invariant chain trimers is rapid and is the first intermediate in the assembly of a nine-chain alpha beta-invariant chain complex. With time, three higher molecular weight complexes are progressively formed. These correspond to an invariant chain trimer with one alpha beta dimer, two alpha beta dimers, and three alpha beta dimers, respectively. No free alpha beta dimers are detectable early in biosynthesis. However, beginning at 2 h of chase, alpha beta dimers begin to appear concomitant with the disappearance of the completely assembled alpha beta-invariant chain complex. This conversion is virtually complete by 4 h, and presumably reflects the proteolytic degradation of the invariant chain component of the alpha beta-invariant chain complex and the generation of endosomal alpha beta dimers capable of binding antigenic peptides.