Phosphoantigens and butyrophilin 3A1 induce similar intracellular activation signaling in human TCRVγ9+ γδ T lymphocytes
Phosphoantigens and butyrophilin 3A1 induce similar intracellular activation signaling in human TCRVγ9+ γδ T lymphocytes
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DOI：
10.1016/j.imlet.2014.05.011
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发表时间：
2014-09-01
影响因子：
4.4
通讯作者：
Fournie, Jean-Jacques
中科院分区：
文献类型：
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作者：
Decaup, Emilie;Duault, Caroline;Fournie, Jean-Jacques
表达TCRV γ 9的人γ δ细胞是具有用于癌症免疫治疗的巨大潜力和非常规抗原特异性模式的T淋巴细胞。这些HLA非限制性淋巴细胞对非肽代谢物（磷抗原）和亲丁酸蛋白3A（BTN 3A/CD 277）蛋白具有特异性反应性。然而，对这种高度不同的结构的识别是否触发了相同的激活信号通路仍不清楚。在这里，我们结合了荧光细胞条形码和TCRV γ 9（+）T淋巴细胞的磷酸流分析，以同时比较磷酸化抗原（BrHPP）或抗BTN 3A（单克隆抗体20.1）激活后几种信号磷酸蛋白的水平。该方法表明，涉及ZAP 70、PLC γ 2、Akt、NF κ B p65、MAPK p38和Erk 1的相同途径由这些刺激中的任一种诱导。这些数据有力地表明TCRV γ 9（+）T淋巴细胞通过相同的识别过程检测磷酸化抗原和亲丁酸蛋白A3。(C)2014由Elsevier B. V.出版
Human gamma delta cells expressing TCRV gamma 9 are T lymphocytes with great potential for cancer immunotherapy and unconventional pattern of antigen specificity. These HLA-unrestricted lymphocytes are specifically reactive to non-peptide metabolites (phosphoantigens) and to the butyrophilin 3A (BTN3A/CD277) protein. Whether recognition of such highly different structures trigger the same activation signaling pathway remains unclear, however. Here we combined fluorescent cell barcoding and phosphoflow analysis of TCRV gamma 9(+) T lymphocytes to compare simultaneously the level of several signaling phosphoproteins after activation by phosphoantigen (BrHPP) or by anti-BTN3A (monoclonal antibody 20.1). This approach shows that the same pathways involving ZAP70, PLC gamma 2, Akt, NF kappa B p65, MAPK p38 and Erk1, were induced by either of these stimuli. These data strongly suggest the TCRV gamma 9(+) T lymphocytes detect phosphoantigens and butyrophilin A3 by the same recognition process.(C) 2014 Published by Elsevier B.V.