Kaufman M, Andris F, Leo O
Université Libre de Bruxelles, Centre for Nonlinear Phenomena and Complex Systems, Campus Plaine CP 231, 1050 Brussels, Belgium.
Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3894-9. doi: 10.1073/pnas.96.7.3894.
Interaction of the antigen-specific receptor of T lymphocytes with its antigenic ligand can lead either to cell activation or to a state of profound unresponsiveness (anergy). Although subtle changes in the nature of the ligand or of the antigen-presenting cell have been shown to affect the outcome of T cell receptor ligation, the mechanism by which the same receptor can induce alternative cellular responses is not completely understood. A model for explaining both positive (cell proliferation and cytokine production) and negative (anergy induction) signaling of T lymphocytes is described herein. This model relies on the autophosphorylative properties of the tyrosine kinases associated with the T cell receptor. One of its basic assumptions is that the kinase activity of these receptor-associated enzymes remains above background level after ligand removal and is responsible for cellular unresponsiveness. Using a simple Boolean formalism, we show how the timing of the binding and intracellular signal-transduction events can affect the properties of receptor signaling and determine the type of cellular response. The present approach integrates into a common framework a large body of experimental observations and allows specification of conditions leading to cellular activation or to anergy.
T淋巴细胞的抗原特异性受体与其抗原配体相互作用可导致细胞活化或深度无反应状态（无反应性）。尽管已表明配体或抗原呈递细胞性质的细微变化会影响T细胞受体连接的结果，但同一受体可诱导不同细胞反应的机制尚未完全明了。本文描述了一个用于解释T淋巴细胞阳性（细胞增殖和细胞因子产生）和阴性（无反应性诱导）信号传导的模型。该模型依赖于与T细胞受体相关的酪氨酸激酶的自身磷酸化特性。其基本假设之一是，这些受体相关酶的激酶活性在配体去除后仍高于背景水平，并导致细胞无反应性。使用简单的布尔形式体系，我们展示了结合和细胞内信号转导事件的时间如何影响受体信号传导的特性并决定细胞反应的类型。目前的方法将大量实验观察结果整合到一个通用框架中，并允许确定导致细胞活化或无反应性的条件。
