T lymphocytes need less than 3 min to discriminate between peptide MHCs with similar TCR-binding parameters.
T lymphocytes need less than 3 min to discriminate between peptide MHCs with similar TCR-binding parameters.
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DOI：
10.1002/eji.201445214
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发表时间：
2015-06
影响因子：
5.4
通讯作者：
van der Merwe PA
中科院分区：
文献类型：
--
作者：
Brodovitch A;Shenderov E;Cerundolo V;Bongrand P;Pierres A;van der Merwe PA
T淋巴细胞需要在众多的外源肽和自身肽中检测罕见的同源外源肽。这种区分似乎是基于TCR与其肽-MHC（pMHC）配体结合的动力学，但几乎没有关于处理基本信号事件和决定启动激活所需的最短时间的直接信息。在这里，我们使用干涉反射显微镜来研究表达1G 4 TCR的转染的人Jurkat T细胞与涂覆有5种不同的1G 4 pMHC配体的表面之间的早期相互作用。诱导T细胞产生50%最大IFN-γ所需的pMHC浓度，以及在可溶相或表面结合分子上测量的1G 4-pMHC解离速率，在pMHC之间显示出6至7倍的变化。当T细胞滴到pMHC包被的表面上时，在2分钟的滞后后发生快速扩散。在前45 s期间测量的初始铺展速率和接触面积强烈依赖于所遇到的TCR配体。然而，滞后持续时间并不显着依赖于遇到的配体。此外，铺展似乎是一个全有或全无的过程，铺展细胞的分数与铺展速率和铺展面积密切相关。因此，T细胞可以在2分钟内区分非常相似的TCR配体。
T lymphocytes need to detect rare cognate foreign peptides among numerous foreign and self-peptides. This discrimination seems to be based on the kinetics of TCRs binding to their peptide–MHC (pMHC) ligands, but there is little direct information on the minimum time required for processing elementary signaling events and deciding to initiate activation. Here, we used interference reflection microscopy to study the early interaction between transfected human Jurkat T cells expressing the 1G4 TCR and surfaces coated with five different pMHC ligands of 1G4. The pMHC concentration required for inducing 50% maximal IFN-γ production by T cells, and 1G4-pMHC dissociation rates measured in soluble phase or on surface-bound molecules, displayed six- to sevenfold variation among pMHCs. When T cells were dropped onto pMHC-coated surfaces, rapid spreading occurred after a 2-min lag. The initial spreading rate measured during the first 45 s, and the contact area, were strongly dependent on the encountered TCR ligand. However, the lag duration did not significantly depend on encountered ligand. In addition, spreading appeared to be an all-or-none process, and the fraction of spreading cells was tightly correlated to the spreading rate and spreading area. Thus, T cells can discriminate between fairly similar TCR ligands within 2 min.