6月27日，Nature雜志在線報道了,，利用人工重建反應(yīng)系統(tǒng)研究T細(xì)胞受體介導(dǎo)的T-細(xì)胞免疫反應(yīng)的最新進(jìn)展。
T-細(xì)胞介導(dǎo)的免疫反應(yīng)由T細(xì)胞受體（TCR）與感染細(xì)胞表面的肽結(jié)合主要組織相容性復(fù)合體（pMHC）的相互作用發(fā)起,。這種相互作用T細(xì)胞受體的觸發(fā)細(xì)胞內(nèi)磷酸化,。但是因為T細(xì)胞受體缺乏激酶結(jié)構(gòu)域，使得這種磷酸化的機(jī)制更加撲朔迷離,。
本研究將T細(xì)胞受體及相關(guān)信號分子引入非免疫細(xì)胞中,，由此在這些細(xì)胞與抗原提呈細(xì)胞結(jié)合時，重建了配體特異性信號,。研究表明,，這種配體特異性信號需要磷酸酶和激酶在細(xì)胞膜上隔離開來。一個人工的,，化學(xué)控制的受體系統(tǒng)可產(chǎn)生與TCR - pMHC系統(tǒng)同樣的效果,。這表明胞外蛋白質(zhì)相互作用的結(jié)合能在無跨膜構(gòu)象變化的條件下造成膜蛋白的空間隔離。
這種普適機(jī)制可能擴(kuò)展到其他依賴于外在的激酶的受體,，包括正在開發(fā)的用于腫瘤免疫治療的嵌合抗原受體,。
這一研究對于深入了解T細(xì)胞免疫反應(yīng)的基本機(jī)制，以及開發(fā)更有效的免疫治療試劑都具有重要的意義,。（生物谷bioon.com）
doi:10.1016/j.cell.2011.10.017
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Biophysical mechanism of T-cell receptor triggering in a reconstituted system
John R. James1 & Ronald D. Vale1
A T-cell-mediated immune response is initiated by the T-cell receptor (TCR) interacting with peptide-bound major histocompatibility complex (pMHC) on an infected cell. The mechanism by which this interaction triggers intracellular phosphorylation of the TCR, which lacks a kinase domain, remains poorly understood. Here, we have introduced the TCR and associated signalling molecules into a non-immune cell and reconstituted ligand-specific signalling when these cells are conjugated with antigen-presenting cells. We show that signalling requires the differential segregation of a phosphatase and kinase in the plasma membrane. An artificial, chemically controlled receptor system generates the same effect as TCR–pMHC, demonstrating that the binding energy of an extracellular protein–protein interaction can drive the spatial segregation of membrane proteins without a transmembrane conformational change. This general mechanism may extend to other receptors that rely on extrinsic kinases, including, as we demonstrate, chimaeric antigen receptors being developed for cancer immunotherapy.
