An induced rebinding model of antigen discrimination.
An induced rebinding model of antigen discrimination.
复制标题
DOI：
10.1016/j.it.2014.02.002
复制
发表时间：
2014-04
影响因子：
16.8
通讯作者：
van der Merwe PA
中科院分区：
文献类型：
--
作者：
Dushek O;van der Merwe PA
我们认为pMHC与TCR的结合可以增加（诱导）pMHC的再结合。已发表的研究与诱导再结合模型一致。诱导的再结合提高了T细胞识别抗原的能力。诱导的再结合使3D与2D TCR-pMHC结合参数相关。T细胞必须在丰富的低亲和力“自身”肽MHC配体中检测罕见的高亲和力“外源”肽MHC（pMHC）配体。目前尚不清楚这种显著的歧视是如何实现的。动力学校正机制可以提供所需的特异性，但代价是灵敏度大大降低。许多最近的观察表明，T细胞受体（TCR）的pMHC接合诱导的变化，如聚类和/或构象改变，增强随后的再结合。我们发现，在动力学校正模型中包含诱导重新结合到相同的pMHC增强了TCR识别的灵敏度，同时保留了特异性。此外，诱导的再结合是能够重现惊人的，迄今无法解释的，二维膜结合特性最近报道的TCR。
We propose that pMHC binding to TCR can increase (induce) pMHC rebinding. Published studies are consistent with an induced rebinding model. Induced rebinding improves the ability of T cells to discriminate antigens. Induced rebinding relates 3D to 2D TCR–pMHC binding parameters. T cells have to detect rare high-affinity ‘foreign’ peptide MHC (pMHC) ligands among abundant low-affinity ‘self’-peptide MHC ligands. It remains unclear how this remarkable discrimination is achieved. Kinetic proofreading mechanisms can provide the required specificity but only at the expense of much reduced sensitivity. A number of recent observations suggest that pMHC engagement of T cell receptors (TCRs) induces changes such as clustering and/or conformational alterations that enhance subsequent rebinding. We show that inclusion of induced rebinding to the same pMHC in kinetic proofreading models enhances the sensitivity of TCR recognition while retaining specificity. Moreover, induced rebinding is able to reproduce the striking, and hitherto unexplained, 2D membrane-binding properties recently reported for the TCR.
登录
查看更多内容
影响因子：
32.4
作者：
Fahmy, TM;Bieler, JG;Schneck, JP
通讯作者：
Schneck, JP
影响因子：
64.8
作者：
Daniels, Mark A.;Teixeiro, Emma;Palmer, Ed
通讯作者：
Palmer, Ed
DOI：
10.1073/pnas.0700411104
发表时间：
2007-11-06
影响因子：
11.1
作者：
James, John R.;White, Samuel S.;Klenerman, David
通讯作者：
Klenerman, David
影响因子：
3.4
作者：
Robert, Philippe;Aleksic, Milos;van der Merwell, P. Anton
通讯作者：
van der Merwell, P. Anton
DOI：
10.1073/pnas.92.11.5042
发表时间：
1995-05-23
影响因子：
11.1
作者：
MCKEITHAN, TW
通讯作者：
MCKEITHAN, TW