The T-cell accessory molecule CD4 recognizes a monomorphic determinant on isolated Ia.
The T-cell accessory molecule CD4 recognizes a monomorphic determinant on isolated Ia.
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T 细胞辅助分子 CD4 识别分离的 Ia 上的单态决定簇。
DOI：
10.1073/pnas.85.15.5629
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发表时间：
1988
影响因子：
11.1
通讯作者：
Marrack,P
中科院分区：
文献类型：
--
作者：
Gay,D;Buus,S;Pasternak,J;Kappler,J;Marrack,P
膜蛋白 CD4 通常存在于对与 II 类主要组织相容性复合物 (MHC; Ia) 蛋白相关的抗原具有特异性的成熟 T 细胞上。这种相关性表明，CD4 与抗原呈递细胞 (APC) 上 Ia 分子的单态区域结合，并通过增强 T 细胞和 APC 之间的相互作用，或相反地，通过将负信号转导至 T 细胞来发挥作用。为了解决这个假设，我们利用了来自一种不寻常的 T 杂交体的亚系，该杂交体受到 I 类 MHC 限制，但也受到 CD4+ 的限制。通过将纯化的MHC蛋白整合到平面膜系统中，我们发现不同的Ia分子可以极大地增强这种I类限制性T杂交体的CD4+而非CD4-变体响应分离的I类分子的能力。 T 细胞上同时表达 CD4 和平面膜上四种不同 Ia 蛋白中的任何一种可以强烈增强 T 细胞反应，从而支持 CD4 与 Ia 分子的单态区域结合并增加 T 细胞与其靶标相互作用的亲合力的观点。
The membrane protein CD4 is commonly found on mature T cells specific for antigen in association with class II major histocompatibility complex (MHC; Ia) proteins. This correlation has led to the suggestion that CD4 binds to a monomorphic region of the Ia molecule on the antigen-presenting cell (APC) and functions either by enhancing interaction between the T cell and the APC, or conversely, by transducing negative signals to the T cell. To address this hypothesis, we have made use of sublines from an unusual T hybrid that is class I MHC restricted but also CD4+. By incorporating purified MHC proteins into a planar membrane system, we show that different Ia molecules can greatly enhance the ability of a CD4+ but not a CD4- variant of this class I-restricted T hybrid to respond to isolated class I molecules. T-cell responses can be strongly augmented by the concurrent expression of CD4 on the T cell and any of four different Ia proteins on planar membranes, thus supporting the idea that CD4 binds to a monomorphic region of the Ia molecule and increases the avidity with which the T cell can interact with its target.