Vγ9Vδ2效應(yīng)T細(xì)胞裂解細(xì)胞響應(yīng)于含有小分子磷，提供一個(gè)獨(dú)一無(wú)二的路線(xiàn) 靈長(zhǎng)類(lèi)去除感染或惡性細(xì)胞。然而，觸發(fā)機(jī)制仍然不明確。我們研究了溶解的人 Vγ9Vδ2效應(yīng)T細(xì)胞反應(yīng)介導(dǎo)的自然發(fā)生（E4-hydroxy-3-methyl-but-2-enyl）-二磷酸（HMBPP）或合成細(xì)胞滲透性藥物，BIS（匹）（E）- 4-hydroxy-3-methyl-but-2-enyl膦酸。CD27 / CD45RA?類(lèi)似的Th1效應(yīng)細(xì)胞殺死K562靶細(xì)胞通過(guò)一種機(jī)制，可以提高復(fù)合或TCR抗體 和阻斷Src抑制或嗜乳脂蛋白3亞型A1（btn3a1）中斷。預(yù)處理4°C降低HMBPP誘導(dǎo)裂解而沒(méi)有降低裂解誘導(dǎo)的BIS（匹）（E）- 4-hydroxy-3-methyl-but-2-enyl膦酸。在一起，我們的研究結(jié)果表明，HMBPP進(jìn)入靶細(xì)胞內(nèi)化為btn3a1依賴(lài) 裂解Vγ9Vδ2效應(yīng)T細(xì)胞所需的。該前藥的模擬活動(dòng)增強(qiáng)是由于其 能力繞過(guò)入境HMBPP所需的途徑。這些發(fā)現(xiàn)支持內(nèi)部的模型T細(xì)胞觸發(fā) 由btn3a1小分子誘導(dǎo)驅(qū)動(dòng)。
本文由專(zhuān)注于提供生物科技服務(wù)的齊一生物收集整理
原文：
Vγ9Vδ2 effector T cells lyse cells in response to phosphorus-containing small molecules, providing primates a unique route to remove infected or malignant cells. Yet, the triggering mechanisms remain ill defined. We examined lysis mediated by human Vγ9Vδ2 effector T cells in response to the naturally occurring (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate (HMBPP) or a synthetic cell-permeable prodrug, bis (pivaloyloxymethyl) (E)-4-hydroxy-3-methyl-but-2-enyl phosphonate. CD27+/CD45RA? Th1-like effector cells killed K562 target cells through a mechanism that could be enhanced by either compound or TCR Ab and blocked by Src inhibition or butyrophilin 3 isoform A1 (BTN3A1) disruption. Pretreatment at 4°C decreased HMBPP-induced lysis but did not reduce lysis induced by bis (pivaloyloxymethyl) (E)-4-hydroxy-3-methyl-but-2-enyl phosphonate. Together, our results show that internalization of HMBPP into target cells is required for BTN3A1-dependent lysis by Vγ9Vδ2 effector T cells. The enhanced activity of the prodrug analog is due to its ability to bypass the pathways required for entry of HMBPP. These findings support an inside-out model of T cell triggering driven by small-molecule induction of BTN3A1.
本文由專(zhuān)注于提供生物科技服務(wù)的齊一生物收集整理
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