Janeway C A, Yagi J, Rojo J, Portoles P, Carding S, Luqman M, Bottomly K
Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06510.
Princess Takamatsu Symp. 1988;19:193-208.
T cells expressing the cell surface differentiation antigen CD4 are involved in most immune responses. Our studies address two issues about CD4 T cell responses to antigen: first, how does the T cell receptor come together with its ligand to generate an immune response, and what is the role of the CD4 molecule in this response? Second, are all CD4 T cells identical in their functional activity, and how does the activating signal determine the functional outcome of a response? Our studies outlined below suggest that the T cell receptor and its peptide: class II major histocompatibility complex (MHC) molecule ligand come together in a defined orientation determined in part by the binding of CD4 to both the T cell receptor and its ligand. Our studies suggest that the V beta chain is involved directly in MHC antigen recognition, binding self MHC with low affinity and non-self MHC with high affinity. The selective effect of the Mls locus on V beta expression is believed to reflect the binding of the Mls protein directly to the V beta region. CD4 is described as a co-receptor, forming an inducible part of the T cell receptor and binding to the same class II MHC molecule as that receptor. Studies with both cloned lines and normal CD4 T cell populations suggest the existence of two separable subsets with definable function. One set appears to be specialized for the activation of the humoral immune response, while the other drives the cell-mediated immune responses, particularly those involving the activation of macrophages. These two subsets of CD4 T cells have differential activation requirements, seen particularly in the requirement for interleukin 1 (IL-1) in the activation and clonal expansion of CD4 T cells involved in humoral immunity. This requirement for IL-1 may also be observed in the priming of this subset of CD4 T cells. These studies demonstrate that the optimal activation of CD4+ T cells involves recognition of peptide fragments presented by class II MHC molecules and accessory signals derived from the antigen presenting cells.
表达细胞表面分化抗原CD4的T细胞参与大多数免疫反应。我们的研究探讨了关于CD4 T细胞对抗原反应的两个问题：第一，T细胞受体如何与其配体结合以产生免疫反应，以及CD4分子在该反应中的作用是什么？第二，所有CD4 T细胞在功能活性上是否相同，以及激活信号如何决定反应的功能结果？下面概述的我们的研究表明，T细胞受体及其肽：II类主要组织相容性复合体（MHC）分子配体以一种特定的方向结合在一起，这种方向部分由CD4与T细胞受体及其配体的结合所决定。我们的研究表明，Vβ链直接参与MHC抗原识别，以低亲和力结合自身MHC，以高亲和力结合非自身MHC。Mls基因座对Vβ表达的选择性作用被认为反映了Mls蛋白直接与Vβ区域的结合。CD4被描述为一种共受体，形成T细胞受体的可诱导部分，并与该受体结合相同的II类MHC分子。对克隆系和正常CD4 T细胞群体的研究表明存在两个具有可定义功能的可分离亚群。一组似乎专门用于激活体液免疫反应，而另一组驱动细胞介导的免疫反应，特别是那些涉及巨噬细胞激活的反应。这两个CD4 T细胞亚群具有不同的激活要求，特别是在参与体液免疫的CD4 T细胞的激活和克隆扩增中对白介素1（IL-1）的要求。在该CD4 T细胞亚群的启动中也可能观察到对IL-1的这种要求。这些研究表明，CD4+ T细胞的最佳激活涉及对II类MHC分子呈递的肽片段的识别以及来自抗原呈递细胞的辅助信号。
