The T-cell receptor is not hardwired to engage MHC ligands
The T-cell receptor is not hardwired to engage MHC ligands
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DOI：
10.1073/pnas.1210882109
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发表时间：
2012-11-06
影响因子：
11.1
通讯作者：
Dyson, Julian
中科院分区：
文献类型：
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作者：
Holland, Stephen J.;Bartok, Istvan;Dyson, Julian
已经提出α β T细胞对MHC配体的偏好是T细胞受体（TCR）固有的。同样，当MHC配体参与时，CD 4和CD 8辅助受体通过使Lck与TCR共定位而有助于配体限制。为了确定内在配体偏好的重要性，在体内广泛多样化的生殖系TCR互补决定区。我们表明，在胸腺细胞选择和外周T细胞活化过程中与MHC配体的接合对TCR结构的约束非常小。这样的多功能性更符合机会主义，而不是预先确定的界面形成模式。通过表达含有TCR-γ链生殖系互补决定区的杂合TCR，其有效地与MHC配体接合，实验证实了该假设。
The bias of alpha beta T cells for MHC ligands has been proposed to be intrinsic to the T-cell receptor (TCR). Equally, the CD4 and CD8 coreceptors contribute to ligand restriction by colocalizing Lck with the TCR when MHC ligands are engaged. To determine the importance of intrinsic ligand bias, the germ-line TCR complementarity determining regions were extensively diversified in vivo. We show that engagement with MHC ligands during thymocyte selection and peripheral T-cell activation imposes remarkably little constraint over TCR structure. Such versatility is more consistent with an opportunist, rather than a predetermined, mode of interface formation. This hypothesis was experimentally confirmed by expressing a hybrid TCR containing TCR-gamma chain germ-line complementarity determining regions, which engaged efficiently with MHC ligands.