T cell receptors: affinities, cross-reactivities, and a conformer model
T cell receptors: affinities, cross-reactivities, and a conformer model
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DOI：
10.1016/j.molimm.2003.11.013
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发表时间：
2004-02-01
影响因子：
3.6
通讯作者：
Kranz, DM
中科院分区：
文献类型：
--
作者：
Holler, PD;Kranz, DM
基于小鼠 CTL 克隆 2C 的 T 细胞受体和其他 TCR 的发现，我们提出了一个可以解释 T 细胞识别简并性的模型。这种“构象模型”认为，单个 TCR 存在于多种处于平衡状态的构象中。该模型符合 (1) 与 2CTCR 和其他 TCR 结合的多个配体的表征，(2) 各种 2C TCR 突变体的结合特性和预测的结构特征，包括通过定向进化分离的更高亲和力变体，以及 (3) TCR 和抗体的三维结构，重点是具有相同一级氨基酸序列的蛋白质所表现出的构象多样性。我们认为，多种构象异构体的优点（例如单个 T 细胞识别许多不同配体的能力）超过缺点（例如较低的 TCR 亲和力和可能的 T 细胞敏感性；与结构不相关的自身配体的有害交叉反应性）。 (C) 2003 Elsevier Ltd. 保留所有权利。
Based on findings with the T cell receptor from mouse CTL clone 2C, and other TCRs, we propose a model that could account for degeneracy of T cell recognition. This "conformer model" holds that a single TCR exists in multiple conformations that are in equilibrium. The model is consistent with (1) the characterization of multiple ligands that bind to the 2CTCR, and other TCRs, (2) the binding properties and predicted structural features of various 2C TCR mutants, including higher affinity variants isolated by directed evolution, and (3) the three-dimensional structures of TCRs and antibodies, with emphasis on the conformational diversity exhibited by proteins with the same primary amino acid sequence. We propose that the advantages of multiple conformers (e.g. ability of a single T cell to recognize many different ligands) outweigh the disadvantages (e.g. lower TCR affinity and possibly T cell sensitivity; detrimental cross-reactivity with structurally unrelated self-ligands). (C) 2003 Elsevier Ltd. All rights reserved.