KINETIC PROOFREADING IN T-CELL RECEPTOR SIGNAL-TRANSDUCTION
KINETIC PROOFREADING IN T-CELL RECEPTOR SIGNAL-TRANSDUCTION
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DOI：
10.1073/pnas.92.11.5042
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发表时间：
1995-05-23
影响因子：
11.1
通讯作者：
MCKEITHAN, TW
中科院分区：
文献类型：
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作者：
MCKEITHAN, TW
与其他具有内在或相关蛋白酪氨酸激酶活性的细胞表面受体一样，T细胞受体复合物在配体结合后但在传递信号之前经历许多修饰，包括酪氨酸磷酸化步骤。对这些修饰的要求在配体结合和受体信号传导之间引入了时间滞后。提出了一种T细胞受体的模型，其中该特征大大增强了受体区分外来抗原和自身抗原的能力，仅具有适度较低的亲和力。所提出的方案是一种动力学校对的形式，已知对于蛋白质和DNA合成的保真度至关重要。还描述了该方案的一个变体，其中需要形成大的聚集体可能导致T细胞活化的特异性的进一步增强。通过这些机制，不同亲和力的配体可能会引发定性不同的信号。
Like other cell-surface receptors with intrinsic or associated protein-tyrosine kinase activity, the T-cell receptor complex undergoes a number of modifications, including tyrosine phosphorylation steps, after ligand binding but before transmitting a signal. The requirement for these modifications introduces a temporal lag between ligand binding and receptor signaling. A model for the T-cell receptor is proposed in which this feature greatly enhances the receptor's ability to discriminate between a foreign antigen and self-antigens with only moderately lower affinity. The proposed scheme is a form of kinetic proofreading, known to be essential for the fidelity of protein and DNA synthesis. A variant of this scheme is also described in which a requirement for formation of large aggregates may lead to a further enhancement of the specificity of T-cell activation. Through these mechanisms, ligands of different affinity potentially may elicit qualitatively different signals.