SYNERGISM IN THE ACTIVATION OF HUMAN CD8 T-CELLS BY CROSS-LINKING THE T-CELL RECEPTOR COMPLEX WITH THE CD8 DIFFERENTIATION ANTIGEN
SYNERGISM IN THE ACTIVATION OF HUMAN CD8 T-CELLS BY CROSS-LINKING THE T-CELL RECEPTOR COMPLEX WITH THE CD8 DIFFERENTIATION ANTIGEN
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DOI：
10.1073/pnas.83.21.8298
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发表时间：
1986-11-01
影响因子：
11.1
通讯作者：
EICHMANN, K
中科院分区：
文献类型：
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作者：
EMMRICH, F;STRITTMATTER, U;EICHMANN, K
通过将T细胞受体复合物（Ti/CD 3）与抗CD 3（T3）抗体（例如OKT 3）以及白细胞介素2交联，可以激活静息的人T细胞并诱导其增殖。在这里，我们描述了另一种单克隆抗CD 3抗体（BMA 030）的功能特性，以各种方式交联，只有微弱的刺激辅助细胞耗尽的T细胞培养。然而，当与抗CD 4或抗CD 8抗体交联时，观察到相应亚群的显著增强的增殖。我们集中于CD 8细胞的分析，并发现BMA 030与抗CD 8（T811）交联在一起时，诱导的增殖比单独的BMA 030高100倍以上，而与其它T细胞膜抗原（HLA-A、B或CD 5）的抗体交联不提供或提供微弱的协同信号。当两种抗体中仅一种（BMA 030或T811）交联而另一种以可溶性形式应用时，没有协同效应。相反，当以可溶形式应用时，单独的两种抗体中的每一种都抑制由交联抗体诱导的活化。T细胞分化抗原CD 8与CD 8 T细胞的主要组织相容性复合体（MHC）I类限制性特异性有关。在其他实验室的先前工作中，仅注意到可溶性抗CD 8抗体的负面影响。相反，我们的研究结果表明，Ti/CD 3和CD 8之间的交联可能是成熟CD 8细胞活化的关键事件。我们假设，在抗原诱导的T细胞活化中，CD 8和Ti/CD 3通过它们同时结合I类相关结构而交联。这种机制，如果需要在早期T细胞个体发育增殖，可以产生一个选择性的压力，CD 8细胞识别I类相关抗原。
Resting human T cells can be activated and induced to proliferate by cross-linking the T-cell receptor complex (Ti/CD3) with anti-CD3 (T3) antibodies, such as OKT3, together with interleukin 2. Here we describe functional properties of another monoclonal anti-CD3 antibody (BMA 030) that, cross-linked in various ways, only weakly stimulates accessory-cell-depleted T-cell cultures. However, when cross-linked to anti-CD4 or anti-CD8 antibodies a markedly enhanced proliferation of the corresponding subpopulation is observed. We have concentrated on the analysis of CD8 cells and have found that BMA 030, when cross-linked together with anti-CD8 (T811), induced proliferation more than 100-fold greater than BMA 030 alone, whereas cross-linking with antibodies to other T-cell membrane antigens (HLA-A, B, or CD5) provided no or marginal synergistic signals. There was no synergistic effect when only one of the two antibodies, BMA 030 or T811, was cross-linked and the other was applied in soluble form. In contrast, each of the two antibodies alone, when applied in soluble form, inhibited activation induced by the cross-linked antibodies. The T-cell differentiation antigen CD8 has been implicated in the major histocompatibility complex (MHC) class I restricted specificity of CD8 T cells. In previous work from other laboratories only the negative influences of soluble anti-CD8 antibodies have been noted. In contrast, our results suggest that cross-linking between Ti/CD3 and CD8 may be a critical event in the activation of mature CD8 cells. We hypothesize that, in antigen-induced T-cell activation, CD8 and Ti/CD3 become cross-linked by their simultaneous binding to class I-associated structures. Such a mechanism, if required for proliferation in early T-cell ontogeny, could generate a selective pressure for CD8 cells to recognize class I-associated antigens.