PD-L1疫苗中引入不同免疫原性氨基酸对T细胞亚群分化的影响  

Effects of different immunogenic amino acids in PD-L1 vaccine on the differ⁃entiation of T cell subsets

作　　者：陈红梅 康彦良 刘利 姚文兵 田浤 CHEN Hongmei;KANG Yanliang;LIU Li;YAO Wenbing;TIAN Hong(Jiangsu Key Laboratory of Druggability of Biopharmaceuticals,School of Life Science and Technology,China Pharmaceutical University,Nanjing 210009,China)

机构地区：[1]中国药科大学生命科学与技术学院,江苏省生物药物成药性研究重点实验室,南京210009

出　　处：《中国药科大学学报》2020年第3期349-356,共8页Journal of China Pharmaceutical University

基　　金：国家自然科学基金资助项目(No.81573222,No.81673343,No.91753112)。

摘　　要：为了比较内源性的3-硝基酪氨酸与非天然的4-硝基苯丙氨酸在PD-L1疫苗中的引入对T细胞亚群分化的影响,利用遗传密码扩充技术,将这两种免疫原性氨基酸分别引入到PD-L1疫苗的相同位点,获得具有3-硝基酪氨酸以及4-硝基苯丙氨酸的两种PD-L1突变体。用这两种突变体免疫小鼠,分析对小鼠脾脏T细胞亚群分化的影响。流式细胞术检测结果显示,4-硝基苯丙氨酸在PD-L1疫苗中的引入可促进Th1细胞的极化,同时降低Treg细胞的比例,3-硝基酪氨酸的引入对Th1细胞的极化无影响,同时能显著提高Treg和Th17细胞的比例。二者在PD-L1疫苗中的引入均能促进脾脏CD8+T细胞的应答,其中含有4-硝基苯丙氨酸的PD-L1突变体应答效果更强。实验结果表明,与内源性的3-硝基酪氨酸在PD-L1疫苗中的引入相比,非天然的4-硝基苯丙氨酸更适合用于肿瘤疫苗的设计。To compare the effects of endogenous 3-nitrotyrosine and non-natural 4-nitrophenylalanine in PD-L1 vaccine on the differentiation of T cell subsets,two immunogenic amino acids were introduced into the same site of PD-L1 vaccine.Two PD-L1 mutants with 3-nitrotyrosine and 4-nitrophenylalanine were obtained,respectively,using genetic code expansion technology.Mice were immunized with these two mutants,and their effects on the differentiation of T cell subsets in spleen were analyzed.The results of flow cytometry showed that the introduc⁃tion of 4-nitrophenylalanine in PD-L1 vaccine could promote the polarization of Th1 cells while reducing the pro⁃portion of Treg cells;the introduction of 3-nitrotyrosine had no effect on the polarization of Th1 cells,while signifi⁃cantly increasing the proportion of Treg and Th17 cells.The introduction of both into PD-L1 vaccine could pro⁃mote the response of CD8+T cells in spleen,and the response of PD-L1 mutant containing 4-nitrophenylalanine was stronger.In summary,the non-natural 4-nitrophenylalanine is more suitable for the design of tumor vaccines as compared with endogenous 3-nitrotyrosine.

关 键 词：PD-L1 疫苗 3-硝基酪氨酸 4-硝基苯丙氨酸 T细胞亚群 

分 类 号：R967[医药卫生—药理学]