Gunter K C, Kroczek R A, Shevach E M, Germain R N
J Exp Med. 1986 Feb 1;163(2):285-300. doi: 10.1084/jem.163.2.285.
The interaction of certain mAbs with the Thy-1 molecules of murine T lymphocytes leads to cell activation and proliferation. To examine the signal transduction mechanism underlying this process and to determine what, if any, relationship exists between Thy-1-dependent triggering and T cell activation mediated through the T3-antigen receptor (T3-Ti) complex, a genomic clone of murine Thy-1.2 was isolated and transfected into the human T cell tumor, Jurkat. The transfected gene was actively transcribed in these human cells and high levels of Thy-1.2 glycoprotein were found on the cell membrane. Although certain mAbs to Thy-1.2 failed to bind to the Thy-1 transfected Jurkat cells, several known mitogenic anti-Thy-1 mAbs did react, and in the presence of phorbol ester, induced IL-2 secretion. One Thy-1+ transfectant out of five failed to produce IL-2 in response to anti-T3/Ti antibodies even though it retained the ability to increase intracytoplasmic calcium concentration [( Ca2+]i) in response to these ligands. A Thy-1 negative revertant of this cell regained anti-T3/Ti reactivity, suggesting a regulatory defect in signal transmission via T3/Ti in the original transfectant. These data confirm the ability of Thy-1 to act as an activation receptor for T cells. They reveal a potential role for changes in [Ca2+]i in this process, in common with other pathways of T cell activation, but also indicate a more complex series of events is involved.
某些单克隆抗体(mAbs)与小鼠T淋巴细胞的Thy-1分子相互作用会导致细胞活化和增殖。为了研究这一过程背后的信号转导机制,并确定Thy-1依赖性触发与通过T3抗原受体(T3-Ti)复合物介导的T细胞活化之间是否存在某种关系,分离出小鼠Thy-1.2的基因组克隆并将其转染到人T细胞肿瘤Jurkat中。转染的基因在这些人细胞中被积极转录,并且在细胞膜上发现了高水平的Thy-1.2糖蛋白。尽管某些针对Thy-1.2的单克隆抗体未能与转染了Thy-1的Jurkat细胞结合,但几种已知的促有丝分裂抗Thy-1单克隆抗体确实有反应,并且在佛波酯存在的情况下,诱导白细胞介素-2(IL-2)分泌。五个Thy-1+转染细胞系中有一个即使保留了对这些配体作出反应增加胞浆钙浓度[Ca2+]i的能力,也未能对抗T3/Ti抗体产生IL-2。该细胞的一个Thy-1阴性回复株恢复了抗T3/Ti反应性,表明原始转染细胞系中通过T3/Ti的信号传递存在调节缺陷。这些数据证实了Thy-1作为T细胞活化受体的能力。它们揭示了[Ca2+]i变化在这一过程中的潜在作用,这与T细胞活化的其他途径相同,但也表明涉及一系列更复杂的事件。