Nössner E, Parham P
Department of Cell Biology, Stanford University, California 94305.
J Exp Med. 1995 Jan 1;181(1):327-37. doi: 10.1084/jem.181.1.327.
Previous studies have shown that immature mouse class I molecules transiently associate with a resident endoplasmic reticulum protein of 88 kD that has been proposed to act as a chaperone for class I assembly. Subsequently, this protein was demonstrated to be identical to calnexin and to associate with immature forms of the T cell receptor complex, immunoglobulin, and human class I HLA heavy chains. In this paper we define further the interaction of human class I HLA heavy chains with chaperone proteins and find key differences with the complexes observed in the mouse system. First, calnexin and immunoglobulin binding protein (BiP) both associate with immature HLA class I heavy chains. The two chaperones are not found within the same molecular complex, suggesting that calnexin and BiP do not interact simultaneously with the same HLA class I heavy chain. Second, only free HLA class I heavy chains, and not beta 2-microglobulin (beta 2m)-associated heavy chains are found associated with the chaperones. Indeed, addition of free beta 2m in vitro induces dissociation of chaperone-class I HLA heavy chain complexes. The kinetics for dissociation of the class I HLA heavy chain-chaperone complexes and for formation of the class I HLA heavy chain-beta 2m complex display a reciprocity that suggests the interactions with chaperone and beta 2m are mutually exclusive. Mouse class I heavy chains expressed in human cells exhibit the mouse pattern of interaction with human chaperones and human beta 2m and not the human pattern, showing the difference in behavior is purely a function of the class I heavy chain sequence.
先前的研究表明，未成熟的小鼠I类分子与一种88kD的内质网驻留蛋白短暂结合，该蛋白被认为是I类组装的伴侣蛋白。随后，该蛋白被证明与钙连蛋白相同，并与T细胞受体复合物、免疫球蛋白和人类I类HLA重链的未成熟形式结合。在本文中，我们进一步定义了人类I类HLA重链与伴侣蛋白的相互作用，并发现与小鼠系统中观察到的复合物存在关键差异。首先，钙连蛋白和免疫球蛋白结合蛋白（BiP）都与未成熟的HLA I类重链结合。在同一分子复合物中未发现这两种伴侣蛋白，这表明钙连蛋白和BiP不会同时与同一条HLA I类重链相互作用。其次，仅发现游离的HLA I类重链与伴侣蛋白结合，而与β2微球蛋白（β2m）相关的重链则未发现与伴侣蛋白结合。事实上，在体外添加游离的β2m会诱导伴侣蛋白-HLA I类重链复合物的解离。I类HLA重链-伴侣蛋白复合物的解离动力学以及I类HLA重链-β2m复合物的形成动力学表现出一种相互关系，这表明与伴侣蛋白和β2m的相互作用是相互排斥的。在人类细胞中表达的小鼠I类重链表现出与人类伴侣蛋白和人类β2m的小鼠相互作用模式，而不是人类模式，这表明行为上的差异纯粹是I类重链序列的函数。
