Role of CD4 and CD8 in enhancing T-cell responses to antigen.
Role of CD4 and CD8 in enhancing T-cell responses to antigen.
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CD4 和 CD8 在增强 T 细胞对抗原反应中的作用。
DOI：
10.1101/sqb.1989.054.01.076
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
Zamoyska,R
中科院分区：
文献类型：
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作者：
Parnes,JR;vonHoegen,P;Miceli,MC;Zamoyska,R
T淋巴细胞可根据其识别特性和其两种细胞表面糖蛋白CD 8或CD 4中任一种的表达分为两个主要亚群。通常，识别与自身I类主要组织相容性复合体（MHC）蛋白结合的外来抗原的T细胞表达CD 8，而识别与II类MHC蛋白结合的外来抗原的T细胞表达CD 4（Swain 1983）。与这种功能细分雅阁，CD 8和CD 4似乎分别作为I类和II类MHC蛋白相对不变区域的受体（Doyle and Strominger 1987; Gay et al. 1988; Norment et al. 1988; Rosenstein et al. 1989）。CD 8和CD 4被称为辅助分子或“共受体”，这是基于它们增加T细胞对抗原的应答的能力。在T细胞受体（TCR）对抗原/MHC的亲和力较低的情况下，这种功能可能非常重要（Marrack et al. 1983; Biddison et al. 1984; Rojo et al. 1989）。为了进一步确定CD 8和CD 4增强T细胞对抗原应答的机制，我们比较了这些蛋白质在能够或不能结合与TCR相同的MHC蛋白质时刺激应答的能力。我们还研究了这些蛋白质的不同结构域的功能作用和人CD 4在小鼠系统中的功能。我们发现，当CD 4和CD 8不能结合与TCR相同的MHC蛋白时，它们增强T细胞反应性的能力是可变的，并且取决于特异性TCR及其对抗原/MHC的亲和力。当这些辅助分子的外部结构域可以结合到与TCR相同的MHC蛋白时，并且当胞质尾能够与T细胞特异性酪氨酸激酶p56 ck相互作用时，发生最佳的反应刺激。最后，我们证明，hCD 4可以刺激反应的II类限制性，抗原特异性小鼠T细胞杂交瘤，尽管存在的抗原呈递细胞上的只有小鼠而不是人的I1类MHC蛋白。
T lymphocytes can be divided into two major subsets based on their recognition properties and their expression of either of two cell-surface glycoproteins, CD8 or CD4. In general, T cells that recognize foreign antigen bound to self class I major histocompatibility complex (MHC) proteins express CD8, whereas those that recognize foreign antigen bound to class II MHC proteins express CD4 (Swain 1983). In accord with this functional subdivision, CD8 and CD4 appear to serve as receptors for relatively invariant regions of class I and class II MHC proteins, respectively (Doyle and Strominger 1987; Gay et al. 1988; Norment et al. 1988; Rosenstein el al. 1989). CD8 and CD4 have been called accessory molecules or" co-receptors" based on their ability to increase T-cell responses to antigen. This function may be of major importance in situations where the affinity of the T-cell receptor (TCR) for antigen/MHC is low (Marrack et al. 1983; Biddison et al. 1984; Rojo et al. 1989). To further define the mechanism (s) by which CD8 and CD4 enhance T-cell responses to antigen, we have compared the ability of these proteins to stimulate responses when they can or cannot bind to the same MHC protein as the TCR. We have also examined the functional roles of different domains of these proteins and the function of human CD4 in a mouse system. We find that the ability of CD4 and CD8 to enhance T-cell responsiveness when they cannot bind to the same MHC protein as the TCR is variable and dependent on the specific TCR and its affinity for antigen/MHC. Optimal stimulation of responses occurs when the external domain of these accessory molecules can bind to the same MHC protein as the TCR and when the cytoplasmic tail is capable of interacting with the T-cell-specific tyrosine kinase p56 ck. Finally, we demonstrate that hCD4 can stimulate responses of a class-II-restricted, antigen-specific mouse T-cell hybridoma despite the presence of only mouse and not human class I1 MHC proteins on the antigen-presenting cells.