Molecular Interactions, T‐Cell Subsets and a Role of the CD4/CD8:p56lck Complex in Human T‐Cell Activation
Molecular Interactions, T‐Cell Subsets and a Role of the CD4/CD8:p56lck Complex in Human T‐Cell Activation
复制标题
分子相互作用、T 细胞亚群以及 CD4/CD8:p56lck 复合物在人类 T 细胞激活中的作用
作者：
C. Rudd;P. Anderson;C. Morimoto;M. Streuli;S. Schlossman
几种T细胞结构能够产生与T细胞增殖相关的细胞内信号。用Ti/CD 3交联CD 2、CD 4和CD 45与这些抗原中的几种可以增强由抗原结合到Ti/CD 3复合物诱导的最小信号。重要的是，这些调节结构中的一些（CD 4、CD 8和CD 45）也在具有不同活化要求和功能程序（辅助、抑制、抑制-诱导和细胞毒性功能）的T细胞亚群上表达。CD 4 + CD 45 RA+（2 H4+）亚群对自身Ia反应良好，对可溶性抗原反应较差，具有抑制-诱导功能。CD 4 + CD 45 RA-（4 B4+）的相互亚群优先被可溶性回忆抗原激活并具有辅助功能。这些亚群中的每一个都可以通过CD 45抗原的差异表达来区分。重要的是，与两种CD 45亚型的N-末端附近的特定区域反应的抗2 H4抗体可以有效地阻断其功能。交联的CD 4与Ti/CD 3复合物优先激活的CD 4 + CD 45 + RA-亚群，而可溶性抗体CD 2优先影响的CD 45-CD 45 RA+亚群。因此，CD 3和CD 4在CD 4 + CD 45 RA-亚群的活化过程中更有效地协同作用，这一结果与该亚群对回忆抗原应答的能力一致。CD 4、CD 8和CD 45抗原的调节作用可能由蛋白质酪氨酸磷酸化和去磷酸化的相互作用网络介导。我们已经表明，CD 4和CD 8抗原与T细胞特异性蛋白酪氨酸激酶（p56 lck）。p56 LCK是具有激活和转化哺乳动物细胞的能力的蛋白酪氨酸激酶家族的成员。CD 4/CD 8：p56 lck复合物具有催化活性，如其磷酸化Ti/CD 3复合物的各种成员的能力所示。相比之下，CD 45抗原在其胞内结构域内具有蛋白酪氨酸磷酸酶活性，并被假定通过与CD 4/CD 8：p56 lck及其潜在底物的调节相互作用发挥功能。因此，CD 4 + CD 45 RA +/-亚群对各种刺激的反应差异以及具有不同免疫调节程序的T细胞亚群的扩增可能受酪氨酸介导的事件途径控制。
Several T-cell structures are capable of generating intracellular signals linked to T-cell proliferation. Crosslinking of CD2, CD4 and CD45 with Ti/CD3 to several of these antigens can augment the minimal signal induced by antigen binding to the Ti/CD3 complex. Importantly, some of these regulatory structures (CD4, CD8 and CD45) are also expressed on subsets of T cells with distinct activation requirements and functional programs (helper, suppressor, suppressor-inducer and cytotoxic function). The CD4+ CD45RA+ (2H4+) subset responds well to self-Ia, poorly to soluble antigen and possesses suppressor-inducer function. A reciprocal subset CD4+ CD45RA- (4B4+) is preferentially activated by soluble recall antigens and possesses helper function. Each of these subsets can be distinguished by virtue of the differential expression of CD45 antigens. Importantly, the anti-2H4 antibody which reacts with a specific region near the N-terminus of two CD45 isoforms can effectively block its function. Crosslinking of CD4 with the Ti/CD3 complex preferentially activated the CD4+ CD45+ RA- subset, while soluble antibodies to CD2 preferentially affected the CD45 CD45RA+ subset. Thus, CD3 and CD4 more effectively synergize in the activation process on the CD4+ CD45RA- subset, a result consistent with the ability of this subpopulation to respond to recall antigens. The regulatory role of the CD4, CD8 and CD45 antigens may be mediated by an interactive network of protein-tyrosine phosphorylation and dephosphorylation. We have shown the CD4 and CD8 antigens to be associated with the T cell-specific protein-tyrosine kinase (p56lck). p56lck is a member of a family of protein-tyrosine kinases with an established ability to activate and transform mammalian cells. The CD4/CD8:p56lck complex is catalytically active as shown by its ability to phosphorylate various members of the Ti/CD3 complex. By contrast, the CD45 antigens possess protein-tyrosine phosphatase activity within their intracellular domains and are postulated to function by virtue of a regulatory interaction with CD4/CD8:p56lck and its potential substrates. Thus, the differences in the response of the CD4+ CD45RA+/- subsets to various stimuli and the expansion of T-cell subsets with distinct immunoregulatory programs may be governed by a pathway of tyrosine-mediated events.
登录
查看更多内容
鉴定人类白细胞共同抗原上 2H4 表位表达所需的序列。
DOI：
10.1084/jem.166.5.1567
发表时间：
1987
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Streuli,M;Matsuyama,T;Morimoto,C;Schlossman,SF;Saito,H
通讯作者：
Saito,H
儿童 T 淋巴细胞恶性肿瘤的胸腺细胞和母细胞中 Leu-4 (T3) 抗原的表面和细胞质表达之间的不一致。
DOI：
10.1172/jci111954
发表时间：
1985
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Link,MP;Stewart,SJ;Warnke,RA;Levy,R
通讯作者：
Levy,R
DOI：
10.1016/s0021-9258(18)32549-3
发表时间：
1983-04
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Jannie Borst;Stephen Alexander;John Elder;Cox TerhorstSn
通讯作者：
Jannie Borst;Stephen Alexander;John Elder;Cox TerhorstSn
证明白细胞共同抗原CD45是一种蛋白酪氨酸磷酸酶。
影响因子：
2.9
作者：
Tonks,NK;Charbonneau,H;Diltz,CD;Fischer,EH;Walsh,KA
通讯作者：
Walsh,KA
%20CD3%20和%20CD4的%20的共调制。%20%20CD4%20和%20之间的%20a%20特异性%20关联%20的证据%20大约%205%%20of%20the%20CD3:T%20cell%20receptor%20complexes%20on%20helper%
DOI：
--
发表时间：
1988
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Anderson,P;Blue,ML;Schlossman,SF
通讯作者：
Schlossman,SF