Disruption of the CD4-major histocompatibility complex class II interaction blocks the development of CD4(+) T cells in vivo.
Disruption of the CD4-major histocompatibility complex class II interaction blocks the development of CD4(+) T cells in vivo.
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CD4-主要组织相容性复合物 II 类相互作用的破坏会阻碍体内 CD4(+) T 细胞的发育。
DOI：
10.1073/pnas.95.8.4493
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发表时间：
1998
影响因子：
11.1
通讯作者：
Doyle,C
中科院分区：
文献类型：
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作者：
Riberdy,JM;Mostaghel,E;Doyle,C
本报告中提出的实验旨在专门检查 CD4-主要组织相容性复合物 (MHC) II 类相互作用在体内 T 细胞发育过程中的作用。我们已经培育出表达 II 类分子的转基因小鼠，这些分子不能与 CD4 相互作用，但能够将肽呈递给 T 细胞受体。通过注射编码野生型 I-Aβb 蛋白的转基因构建体或编码旨在特异性破坏与 CD4 分子结合的突变的构建体，在 Aβ 基因敲除小鼠中重建 MHC II 类表达。我们证明 I-Ab β2 结构域中的突变 EA137 和 VA142 足以破坏体内 CD4-MHC II 类相互作用。此外，我们表明，这种相互作用对于有效选择成熟 CD4+T 辅助细胞的完整库至关重要，因为表达 EA137/VA142 突变体 I-Ab 的动物中常规 CD4+T 细胞的数量急剧减少，这是由于未能积极选择突变 I-Ab 上的转基因 AND T 细胞受体而证明的。这些结果强调了 CD4-II 类相互作用在成熟外周 CD4+T 细胞发育中的重要性。
The experiments presented in this report were designed to specifically examine the role of CD4–major histocompatibility complex (MHC) class II interactions during T cell developmentin vivo. We have generated transgenic mice expressing class II molecules that cannot interact with CD4 but that are otherwise competent to present peptides to the T cell receptor. MHC class II expression was reconstituted in Aβ gene knock-out mice by injection of a transgenic construct encoding either the wild-type I-Aβbprotein or a construct encoding a mutation designed to specifically disrupt binding to the CD4 molecule. We demonstrate that the mutation, EA137 and VA142 in the β2 domain of I-Ab, is sufficient to disrupt CD4–MHC class II interactionsin vivo. Furthermore, we show that this interaction is critical for the efficient selection of a complete repertoire of mature CD4+T helper cells as evidenced by drastically reduced numbers of conventional CD4+T cells in animals expressing the EA137/VA142 mutant I-Aband by the failure to positively select the transgenic AND T cell receptor on the mutated I-Ab. These results underscore the importance of the CD4–class II interaction in the development of mature peripheral CD4+T cells.