Organization of the resting TCR in nanoscale oligomers
Organization of the resting TCR in nanoscale oligomers
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DOI：
10.1111/imr.12019
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发表时间：
2013-01
影响因子：
8.7
通讯作者：
W. Schamel;B. Alarcón
中科院分区：
文献类型：
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作者：
W. Schamel;B. Alarcón
尽管T细胞抗原受体(TCR)对其多肽/主要组织相容性复合体(PMHC)配体的亲和力较低，但T细胞对其抗原非常敏感。如果我们认为TCR可以被组织成预先存在的低聚物或纳米团簇，这个悖论就可以解决。这种结构可以通过增加TCR-pMHC相互作用的功能亲和力(亲和力)以及允许单个TCR之间的协同作用来改善抗原识别。大约有20个TCR紧密地排列在这些纳米簇中，通常是以线性的方式，这样的结构可以反映一个相对普遍的现象：膜受体在质膜的特定区域非随机集中，称为蛋白质岛。TCR与纳米团簇的结合可以解释pMHC-TCR在二维和三维体系中相互作用的增强动力学，但它们的存在也要求对基于pMHC诱导的TCR聚集的TCR触发模型进行修订。有趣的是，B细胞受体和FcεRI也被证明形成了纳米簇，这表明预先存在的受体寡聚体的形成可能在免疫系统中得到广泛应用。
Despite the low affinity of the T‐cell antigen receptor (TCR) for its peptide/major histocompatibility complex (pMHC) ligand, T cells are very sensitive to their antigens. This paradox can be resolved if we consider that the TCR may be organized into pre‐existing oligomers or nanoclusters. Such structures could improve antigen recognition by increasing the functional affinity (avidity) of the TCR–pMHC interaction and by allowing cooperativity between individual TCRs. Up to approximately 20 TCRs become tightly apposed in these nanoclusters, often in a linear manner, and such structures could reflect a relatively generalized phenomenon: the non‐random concentration of membrane receptors in specific areas of the plasma membrane known as protein islands. The association of TCRs into nanoclusters can explain the enhanced kinetics of the pMHC–TCR interaction in two dimensional versus three dimensional systems, but also their existence calls for a revision of the TCR triggering models based on pMHC‐induced TCR clustering. Interestingly, the B‐cell receptor and the FcεRI have also been shown to form nanoclusters, suggesting that the formation of pre‐existing receptor oligomers could be widely used in the immune system.