Kappes Dietmar J, He Xi, He Xiao
Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Immunol Rev. 2006 Feb;209:237-52. doi: 10.1111/j.0105-2896.2006.00344.x.
The molecular basis of CD4:CD8 lineage commitment, in particular the mechanism by which the precise correlation between lineage choice and T-cell receptor (TCR) specificity toward class I or II major histocompatibility complex is achieved, remains controversial. Both stochastic/selective and instructive models in various forms have been proposed to explain this correlation. The two main experimental approaches previously employed to elucidate this process have focused on the beginning and end of the process, i.e. the influence of TCR signaling and the alternate transcriptional control of the CD4 and CD8 loci during commitment. The recent finding that the transcription factor Th-POK is necessary and sufficient for CD4 commitment has now provided a direct entry point for studying the intracellular pathways that govern lineage commitment. Here, we review data leading to the identification and characterization of this factor and discuss the implications of these studies in the context of current models of lineage commitment.
CD4⁺:CD8⁺谱系定向的分子基础，尤其是实现谱系选择与T细胞受体（TCR）针对I类或II类主要组织相容性复合体的特异性之间精确关联的机制，仍存在争议。已经提出了各种形式的随机/选择模型和指导模型来解释这种关联。先前用于阐明这一过程的两种主要实验方法集中在该过程的起始和结束阶段，即TCR信号传导的影响以及定向过程中CD4和CD8基因座的交替转录控制。最近发现转录因子Th-POK对于CD4定向是必需且充分的，这为研究控制谱系定向的细胞内途径提供了一个直接切入点。在这里，我们回顾了导致该因子被鉴定和表征的数据，并在当前谱系定向模型的背景下讨论了这些研究的意义。
