Lancki D W, Ma D I, Havran W L, Fitch F W
Immunol Rev. 1984 Oct;81:65-94. doi: 10.1111/j.1600-065x.1984.tb01105.x.
We have discussed four specific models which provide different kinds of information about the requirements for T cell activation. The first utilized a CTL clone designated L3, which is reactive specifically with Ld alloantigen, to study the involvement of the associative recognition structure Lyt-2 in cytolysis. The apparent requirements for activation of this CTL clone differ depending on whether the target cells bear specific alloantigen or are hybridoma cells which express on their cell surface a clonotypic antibody which reacts specifically with the L3 T cell receptor for antigen. When the antigen receptor reacts with alloantigen on the allogeneic target cell, cytolysis is inhibited by anti-Lyt-2 antibody. However, when the clonotypic antibody of the target cell reacts with the antigen receptor of the T cell, cytolysis is much less inhibited by anti-Lyt-2 antibody. The antigen receptor seems to be responsible for the specificity of both these interactions but the avidity of the interaction between CTL and target cell seems to differ in the two situations. Evidence that participation of the L3T4 associative recognition structure on HTL is less important for cloned T cells which have higher affinity antigen receptors was provided by the second model system which used cloned HTL selected for optimal responses to different concentrations of nominal antigen. Proliferative responses of those clones which responded to lower antigen concentrations were less readily inhibited by anti-L3T4 mAb. Evidence provided by these two model systems is consistent with the concept that associative recognition structures are of lesser importance for T cell activation for those T cells which have higher affinity antigen receptors. In the third model system, we have identified several monoclonal antibodies which augment proliferative response of cloned T cells to sub-optimal amounts of IL-2, probably by reacting with the antigen receptor or with the associated Leu-4/T3 structure. The reactivity patterns of these antibodies indicate that several different epitopes are being recognized. Some appear to be clonotypic although they do not block functional activity of the clone with which they react. Others react with all T clones which we have tested. Several of these react with a cell surface antigen which is expressed at about the same level as the clonotypic structures: these antibodies may react with the murine equivalent of the human Leu-4/T3 molecular complex. One of the "pan-T cell" antibodies which augments IL-2-induced T cell proliferation appears to react with Thy-1; this antibody is similar to one described recently by Gunter et al. (1984).(ABSTRACT TRUNCATED AT 400 WORDS)
我们已经讨论了四种特定模型,它们提供了有关T细胞激活要求的不同类型信息。第一种模型利用了一个名为L3的CTL克隆,它能特异性地与Ld同种异体抗原发生反应,以研究关联识别结构Lyt-2在细胞溶解中的作用。激活这个CTL克隆的明显要求因靶细胞是携带特异性同种异体抗原还是杂交瘤细胞而有所不同,杂交瘤细胞在其细胞表面表达一种与L3 T细胞抗原受体特异性反应的克隆型抗体。当抗原受体与同种异体靶细胞上的同种异体抗原反应时,抗Lyt-2抗体可抑制细胞溶解。然而,当靶细胞的克隆型抗体与T细胞的抗原受体反应时,抗Lyt-2抗体对细胞溶解的抑制作用要小得多。抗原受体似乎决定了这两种相互作用的特异性,但CTL与靶细胞之间相互作用的亲和力在两种情况下似乎有所不同。第二个模型系统提供了证据,表明对于具有更高亲和力抗原受体的克隆T细胞,HTL上L3T4关联识别结构的参与不太重要,该模型系统使用了针对不同浓度的名义抗原选择的用于最佳反应的克隆HTL。那些对较低抗原浓度有反应的克隆的增殖反应较不易被抗L3T4单克隆抗体抑制。这两个模型系统提供的证据与以下概念一致,即对于那些具有更高亲和力抗原受体的T细胞,关联识别结构对T细胞激活的重要性较小。在第三个模型系统中,我们鉴定了几种单克隆抗体,它们可能通过与抗原受体或相关的Leu-4/T3结构反应,增强克隆T细胞对亚最佳量IL-2的增殖反应。这些抗体的反应模式表明正在识别几种不同的表位。有些似乎是克隆型的,尽管它们不会阻断与其反应的克隆的功能活性。其他抗体与我们测试过的所有T克隆反应。其中几种与一种细胞表面抗原反应,该抗原的表达水平与克隆型结构大致相同:这些抗体可能与人类Leu-4/T3分子复合物的小鼠等效物反应。一种增强IL-2诱导的T细胞增殖的“泛T细胞”抗体似乎与Thy-1反应;这种抗体与Gunter等人(1984年)最近描述的一种抗体相似。(摘要截于400字)