Boniface J J, Rabinowitz J D, Wülfing C, Hampl J, Reich Z, Altman J D, Kantor R M, Beeson C, McConnell H M, Davis M M
Department of Microbiology and Immunology, Stanford University, California 94305, USA.
Immunity. 1998 Oct;9(4):459-66. doi: 10.1016/s1074-7613(00)80629-9.
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.
虽然人们对T细胞受体（TCR）参与时T细胞内的信号转导事件了解很多，但信号启动的机制尚不清楚。我们构建了可溶性抗原 - 主要组织相容性复合体（MHC）分子（TCR的天然配体）的特定寡聚体。利用这些寡聚体在体外刺激特定的T细胞，我们发现激动剂肽/MHC配体作为单体无刺激作用，作为二聚体刺激作用最小。同样，部分激动剂配体作为四聚体时活性非常弱。相比之下，能持续与多个TCR结合的三聚体或四聚体激动剂配体是强效刺激物。配体驱动的TCR簇形成似乎是有效激活所必需的，并且有助于解释T细胞的特异性和敏感性。
