Defective major histocompatibility complex class II assembly, transport, peptide acquisition, and CD4+ T cell selection in mice lacking invariant chain expression.
Defective major histocompatibility complex class II assembly, transport, peptide acquisition, and CD4+ T cell selection in mice lacking invariant chain expression.
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缺乏不变链表达的小鼠中有缺陷的主要组织相容性复合物II类组装，运输，肽的采集和CD4+ T细胞的选择。
DOI：
10.1084/jem.177.6.1699
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发表时间：
1993-06-01
期刊：
影响因子：
--
通讯作者：
Robertson EJ
中科院分区：
文献类型：
--
作者：
Bikoff EK;Huang LY;Episkopou V;van Meerwijk J;Germain RN;Robertson EJ
我们使用基因靶向技术制造了缺乏与主要组织相容性复合体（MHC） II类分子相关的不变性链的小鼠。来自这些小鼠的细胞显示出表面II类的显著减少，这是由于II类α链和β链的关联缺陷和高尔基转运明显减少造成的。到达细胞表面的少数II类α / β异二聚体表现为空的或被容易移位的肽占据，并显示出独特的结构。突变的脾细胞呈递完整蛋白抗原的能力有缺陷，但在多肽的存在下刺激增强的反应。这些突变小鼠胸腺和外周CD4+ T细胞的数量大大减少。总的来说，这一惊人的表型表明，在完整的动物中，不变性链在调节MHC II类表达和功能方面起着关键作用。
We used gene targeting techniques to produce mice lacking the invariant chain associated with major histocompatibility complex (MHC) class II molecules. Cells from these mice show a dramatic reduction in surface class II, resulting from both defective association of class II alpha and beta chains and markedly decreased post-Golgi transport. The few class II alpha/beta heterodimers reaching the cell surface behave as if empty or occupied by an easily displaced peptide, and display a distinct structure. Mutant spleen cells are defective in their ability to present intact protein antigens, but stimulate enhanced responses in the presence of peptides. These mutant mice have greatly reduced numbers of thymic and peripheral CD4+ T cells. Overall, this striking phenotype establishes that the invariant chain plays a critical role in regulating MHC class II expression and function in the intact animal.