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II类组织相容性抗原的生物合成与加工

Biosynthesis and processing of class II histocompatibility antigens.

作者信息

Cresswell P, Blum J S, Kelner D N, Marks M S

出版信息

Crit Rev Immunol. 1987;7(1):31-53.

PMID:3545672
Abstract

The class II major histocompatibility antigens at the cell surface exist as heterodimers of alpha and beta subunits. During biosynthesis, these subunits are associated with a third chain, the invariant (I) or I chain. Association with the I chain occurs early in biosynthesis in the rough endoplasmic reticulum and persists during transport through the Golgi apparatus. One of the two alpha subunit N-linked oligosaccharides and the single beta subunit N-linked oligosaccharide are converted to the complex form during Golgi transit. In the human system, both I chain N-linked oligosaccharides can also be processed to the complex form, and at least two O-linked oligosaccharides can be added to the I chain. At some point during transit to the cell surface, class II antigens associate with a proteoglycan bearing chondroitin sulfate side chains. Complexes containing alpha, beta and I chain subunits and the associated proteoglycan accumulate in human B-cell lines treated with the ionophore monensin, an inhibitor of Golgi transport, suggesting that this may be a biosynthetic intermediate in class II antigen transport and assembly. Prior to cell surface expression of class II antigens, the exocytic pathway which they follow intersects the endocytic route, followed by certain ligands internalized by receptor-mediated endocytosis. The I chain appears to dissociate from mature class II alpha, beta dimers prior to their cell surface expression but following the intersection of the exocytic and endocytic pathways.

摘要

细胞表面的II类主要组织相容性抗原以α和β亚基的异二聚体形式存在。在生物合成过程中,这些亚基与第三条链,即不变(I)链或I链相关联。与I链的关联在粗面内质网中生物合成的早期发生,并在通过高尔基体的运输过程中持续存在。两个α亚基N-连接寡糖之一和单个β亚基N-连接寡糖在高尔基体转运过程中转化为复杂形式。在人类系统中,I链的两个N-连接寡糖也可以加工成复杂形式,并且至少两个O-连接寡糖可以添加到I链上。在转运到细胞表面的某个阶段,II类抗原与带有硫酸软骨素侧链的蛋白聚糖结合。含有α、β和I链亚基以及相关蛋白聚糖的复合物在经离子载体莫能菌素(一种高尔基体运输抑制剂)处理的人类B细胞系中积累,这表明这可能是II类抗原运输和组装中的生物合成中间体。在II类抗原细胞表面表达之前,它们所遵循的胞吐途径与内吞途径相交,随后是某些通过受体介导的内吞作用内化的配体。I链似乎在成熟的II类α、β二聚体细胞表面表达之前,但在胞吐和内吞途径相交之后从其解离。

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J Exp Med. 1995 Aug 1;182(2):325-34. doi: 10.1084/jem.182.2.325.
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Am J Pathol. 1988 Oct;133(1):15-21.
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HLA expression in human hepatocellular carcinoma.
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Res Immunol. 1989 Feb;140(2):202-7; discussion 245-8. doi: 10.1016/0923-2494(89)90087-4.
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Invariant chain trimers are sequestered in the rough endoplasmic reticulum in the absence of association with HLA class II antigens.在未与HLA II类抗原结合的情况下,不变链三聚体被隔离在内质网中。
J Cell Biol. 1990 Sep;111(3):839-55. doi: 10.1083/jcb.111.3.839.
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Regulation of the class II-associated invariant chain gene in normal and mutant B lymphocytes.正常和突变B淋巴细胞中II类相关恒定链基因的调控。
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