Lymphocyte Biology Section, Laboratory of Immunology, Trans-NIH Center for Human Immunology (CHI), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1892, USA.
FEBS Lett. 2010 Dec 15;584(24):4814-22. doi: 10.1016/j.febslet.2010.10.027. Epub 2010 Oct 20.
Signaling through the T cell receptor for antigen (TCR) has been studied for years by conventional biochemical means. More recently, attempts have been made to develop computational models of signaling through this receptor, with a specific focus on understanding how this recognition system discriminates between closely related (self and non-self) ligands. Here we discuss recent advances centered on the role of feedback regulation, especially the key finding that a combination of digital and analog control circuits is fundamental to the discrimination properties of the TCR. We end by pointing to future, more biologically accurate models that incorporate spatial aspects of molecular organization in antigen-engaged T lymphocytes with this underlying biochemistry.
多年来，人们一直通过传统的生化手段研究 T 细胞受体（TCR）对抗原的信号转导。最近，人们试图开发通过该受体进行信号转导的计算模型，特别关注如何理解这个识别系统区分密切相关的（自身和非自身）配体。在这里，我们讨论了最近的进展，重点是反馈调节的作用，特别是关键发现，即数字和模拟控制电路的组合对于 TCR 的区分特性是至关重要的。最后，我们指出了未来更符合生物学特性的模型，这些模型将抗原结合的 T 淋巴细胞中的分子组织的空间方面与这种基础生物化学结合起来。
