Critical role for CD8 in T cell receptor binding and activation by peptide/major histocompatibility complex multimers.
Critical role for CD8 in T cell receptor binding and activation by peptide/major histocompatibility complex multimers.
复制标题
DOI：
10.1084/jem.191.2.335
复制
发表时间：
2000-01-17
期刊：
影响因子：
--
通讯作者：
Jameson SC
中科院分区：
文献类型：
--
作者：
Daniels MA;Jameson SC
近期利用主要组织相容性复合体（MHC）/肽四聚体和二聚体的数据表明，T细胞共受体CD4和CD8虽然对T细胞激活很重要，但在促进T细胞受体（TCR）与多价MHC/肽配体结合方面并不起直接作用。相反，当前的一种模型提出，共受体只有在稳定的TCR - MHC/肽复合物已经形成并发出信号之后才会被募集。相比之下，我们利用多聚体I类MHC/肽配体表明，CD8在抗原特异性TCR结合中起着关键作用（在某些情况下是必不可少的）。通过钙动员测量的T细胞激活是由多聚体配体而非单体配体诱导的，并且也显示出对CD8的依赖性。我们使用抗CD8抗体的分析显示，与CD8不同表位的结合既可以阻断也可以增强TCR - MHC/肽的相互作用。当研究与多聚体低亲和力配体（包括TCR拮抗剂）的结合时，这些对TCR与高亲和力激动剂配体结合的影响更加显著。我们的数据对CD8在TCR与MHC/肽配体结合以及T细胞激活中的作用具有重要意义。此外，我们的结果反驳了多聚体MHC/肽配体直接且仅仅与TCR结合的观点；相反，我们的数据强调了CD8对这种结合的关键作用。
Recent data using MHC/peptide tetramers and dimers suggests that the T cell coreceptors, CD4 and CD8, although important for T cell activation, do not play a direct role in facilitating T cell receptor (TCR) binding to multivalent MHC/peptide ligands. Instead, a current model proposes that coreceptors are recruited only after a stable TCR–MHC/peptide complex has already formed and signaled. In contrast, we show using multimeric class I MHC/peptide ligands that CD8 plays a critical (in some cases obligatory) role in antigen-specific TCR binding. T cell activation, measured by calcium mobilization, was induced by multimeric but not monomeric ligands and also showed CD8 dependency. Our analysis using anti-CD8 antibodies revealed that binding to different epitopes of CD8 can either block or augment TCR–MHC/peptide interaction. These effects on TCR binding to high-affinity agonist ligands were even more pronounced when binding to multimeric low-affinity ligands, including TCR antagonists, was studied. Our data have important implications for the role of CD8 in TCR binding to MHC/peptide ligands and in T cell activation. In addition, our results argue against the view that multimeric MHC/peptide ligands bind directly and solely to the TCR; rather, our data highlight a pivotal contribution of CD8 for this association.
登录
查看更多内容
影响因子：
15.3
作者：
Hamad, ARA;O'Herrin, SM;Pardoll, D
通讯作者：
Pardoll, D
影响因子：
64.8
作者：
Alam, SM;Travers, PJ;Gascoigne, NRJ
通讯作者：
Gascoigne, NRJ
影响因子：
32.4
作者：
Boniface, JJ;Rabinowitz, JD;Davis, MM
通讯作者：
Davis, MM
影响因子：
15.3
作者：
ABASTADO, JP;LONE, YC;KOURILSKY, P
通讯作者：
KOURILSKY, P
影响因子：
56.9
作者：
Altman, JD;Moss, PAH;Davis, MM
通讯作者：
Davis, MM