TRANSPORT-PROPERTIES OF FREE AND MHC CLASS II-ASSOCIATED OLIGOMERS CONTAINING DIFFERENT ISOFORMS OF HUMAN INVARIANT CHAIN
TRANSPORT-PROPERTIES OF FREE AND MHC CLASS II-ASSOCIATED OLIGOMERS CONTAINING DIFFERENT ISOFORMS OF HUMAN INVARIANT CHAIN
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DOI：
10.1093/intimm/6.3.439
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发表时间：
1994-03-01
影响因子：
4.4
通讯作者：
CRESSWELL, P
中科院分区：
文献类型：
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作者：
ARUNACHALAM, B;LAMB, CA;CRESSWELL, P
主要组织相容性复合体（MHC） II类分子是α和β亚基的异源二聚体，它们与细胞内的不变链相结合。人类不变量链存在于p33、p35、p41和p43四种形式，是由交替起始翻译和交替剪接共同产生的。不同形式的不变链存在的生物学意义尚不清楚，迄今为止还没有研究比较了所有四种使用一个系统。我们比较了它们的运输特性以及它们将相关MHC II类异源二聚体运输到内吞途径的能力。在这里，我们报道了含有p33和p35或p41和p43的异质低聚物在缺乏II类α和β链的情况下仍然存在于内质网（ER）中。这与先前的报道一致，认为p35和p43共享的n端延伸包含ER保留信号。仅含有p33或p41不变链形式的同源低聚物离开内质网，并在通过高尔基体后被分类到核内体。它们的积累导致核内体增大。p35/p33形式与p43/p41形式交替剪接的周转率的定量表明，后者在内质网和通过高尔基体转运后都更稳定。当第11类分子与p33和p35或p41和p43共表达时，组装的复合物被有效地运输到内吞途径。
Major histocompatibility complex (MHC) class II molecules are heterodimers of alpha, and beta subunits that associate intracellularly with the invariant chain. Human invariant chain exists in four forms, p33, p35, p41, and p43, generated by a combination of alternative initiation of translation and alternative splicing. The biological significance of the existence of the different forms of invariant chain is still unclear and to date no study has compared all four using one system. We have compared them for their transport characteristics and for their ability to transport associated MHC class II heterodimers into the endocytic pathway. Here we report that hetero oligomers containing p33 and p35 or p41 and p43 remain in the endoplasmic reticulum (ER) in the absence of class II alpha and beta chains. This is consistent with earlier reports suggesting that the N-terminal extension shared by p35 and p43 contains an ER retention signal. Homo oligomers containing only the p33 or p41 forms of invariant chain exit the ER and are sorted to endosomes following passage through the Golgi apparatus. Their accumulation leads to enlargement of the endosomes. Quantitation of the turnover rates of the p35/p33 forms with the alternatively spliced p43/p41 forms indicates that the latter are more stable, both in the ER and following transport through the Golgi apparatus. When class 11 molecules are co-expressed with p33 and p35, or p41 and p43, the assembled complex is efficiently transported to the endocytic pathway.