微调T细胞受体信号传导以控制T细胞发育。
Fine-tuning T cell receptor signaling to control T cell development.
作者信息
Fu Guo, Rybakin Vasily, Brzostek Joanna, Paster Wolfgang, Acuto Oreste, Gascoigne Nicholas R J
机构信息
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Singapore 117597.
出版信息
Trends Immunol. 2014 Jul;35(7):311-8. doi: 10.1016/j.it.2014.05.003. Epub 2014 Jun 17.
T cell development from immature CD4(+)CD8(+) double-positive (DP) thymocytes to the mature CD4 or CD8 single-positive (SP) stage requires proper T cell receptor (TCR) signaling. The current working model of thymocyte development is that the strength of the TCR-mediated signal - from little-or-none, through intermediate, to strong - received by the immature cells determines whether they will undergo death by neglect, positive selection, or negative selection, respectively. In recent years, several developmentally regulated, stage-specifically expressed proteins and miRNAs have been found that act like fine-tuners for signal transduction and propagation downstream of the TCR. This allows them to govern thymocyte positive selection. Here, we summarize recent findings on these molecules and suggest new concepts of TCR positive-selection signaling.
T细胞从不成熟的CD4(+)CD8(+)双阳性(DP)胸腺细胞发育到成熟的CD4或CD8单阳性(SP)阶段需要适当的T细胞受体(TCR)信号传导。目前胸腺细胞发育的工作模型是,未成熟细胞接收到的TCR介导信号的强度——从小或无、到中等、再到强——分别决定了它们是通过被忽视而死亡、进行阳性选择还是阴性选择。近年来,人们发现了几种受发育调节、阶段特异性表达的蛋白质和微小RNA,它们就像TCR下游信号转导和传播的微调器。这使它们能够控制胸腺细胞的阳性选择。在这里,我们总结了关于这些分子的最新发现,并提出了TCR阳性选择信号传导的新概念。