Nijenhuis M, Neefjes J
Department of Cellular Biochemistry, The Netherlands Cancer Institute, Amsterdam.
Eur J Immunol. 1994 Jan;24(1):247-56. doi: 10.1002/eji.1830240139.
Endogenous antigen presentation by major histocompatibility complex class II molecules can be understood if class II alpha beta heterodimers bind peptide in the endoplasmic reticulum (ER) before they associate with the invariant chain (Ii). We have studied the assembly of class II molecules from the free alpha, beta and Ii subunits to examine the existence of a class II alpha beta heterodimer as an intermediate in the assembly of class II alpha beta Ii heterotrimers in the ER. In human kidney cell transfectants, the free class II alpha and beta subunits and the class II alpha beta heterodimer are retained in the ER by association with the chaperonin immunoglobulin binding protein (BiP) and Ii is retained through its cytoplasmic tail. Co-expression of Ii results in release of BiP from class II alpha beta complexes and exit of class II alpha beta Ii heterotrimers from the ER. We show that the cytoplasmic tail and the transmembrane region of the class II alpha and beta chain is not essential for proper assembly of the class II alpha beta heterodimer. We followed assembly of the class II alpha beta Ii heterotrimers in wild-type cells. The class II subunits assemble post-translationally. No class II alpha beta heterodimers could be isolated as intermediates in the formation of class II alpha beta Ii heterotrimers, suggesting that peptide binding by class II molecules in the ER is necessarily inefficient.
如果主要组织相容性复合体II类分子在内质网（ER）中与恒定链（Ii）结合之前，其II类αβ异二聚体就结合了肽段，那么内源性抗原呈递就可以得到解释。我们研究了从游离的α、β和Ii亚基组装II类分子的过程，以检验II类αβ异二聚体作为ER中II类αβIi异三聚体组装中间体的存在情况。在人肾细胞转染体中，游离的II类α和β亚基以及II类αβ异二聚体通过与伴侣蛋白免疫球蛋白结合蛋白（BiP）结合而保留在内质网中，而Ii则通过其胞质尾巴被保留。Ii的共表达导致BiP从II类αβ复合物中释放，以及II类αβIi异三聚体从内质网中输出。我们表明，II类α和β链的胞质尾巴和跨膜区域对于II类αβ异二聚体的正确组装并非必不可少。我们追踪了野生型细胞中II类αβIi异三聚体的组装过程。II类亚基在翻译后组装。在II类αβIi异三聚体形成过程中，没有II类αβ异二聚体可以作为中间体被分离出来，这表明内质网中II类分子的肽段结合必然效率低下。
