Initiation of signal transduction through the T cell receptor requires the peptide multivalent engagement of MHC ligands
Initiation of signal transduction through the T cell receptor requires the peptide multivalent engagement of MHC ligands
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DOI：
10.1016/s1074-7613(00)80629-9
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发表时间：
1998-10-01
期刊：
影响因子：
32.4
通讯作者：
Davis, MM
中科院分区：
文献类型：
--
作者：
Boniface, JJ;Rabinowitz, JD;Davis, MM
当T细胞受体（TCR）被激活时，人们对T细胞内的信号传导事件已有很多了解，但信号传导起始的机制尚不清楚。我们构建了明确的可溶性抗原 - 主要组织相容性复合体（MHC）分子的寡聚体，它们是TCR的天然配体。利用这些寡聚体在体外刺激特异性T细胞，我们发现激动剂肽/MHC配体作为单体时无刺激作用，作为二聚体时刺激作用也很弱。同样，一种部分激动剂配体作为四聚体时活性非常弱。相比之下，能够持续结合多个TCR的三聚体或四聚体激动剂配体则是强效刺激物。配体驱动的TCR簇的形成似乎是有效激活所必需的，这有助于解释T细胞的特异性和敏感性。
While much is known about intracellular signaling events in T cells when T cell receptors (TCRs) are engaged, the mechanism by which signaling is initiated is unclear. We have constructed defined oligomers of soluble antigen-major histocompatibility complex (MHC) molecules, the natural ligands for the TCR. Using these to stimulate specific T cells in vitro, we find that agonist peptide/MHC ligands are nonstimulatory as monomers and minimally stimulatory as dimers. Similarly, a partial-agonist ligand is very weakly active as a tetramer. In contrast, trimeric or tetrameric agonist ligands that engage multiple TCRs for a sustained duration are potent stimuli. Ligand-driven formation of TCR clusters seems required for effective activation and helps to explain the specificity and sensitivity of T cells.