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 differentiation of T cell subsets
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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。Abstract: 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 introduction of 4-nitrophenylalanine in PD-L1 vaccine could promote the polarization of Th1 cells while reducing the proportion of Treg cells; the introduction of 3-nitrotyrosine had no effect on the polarization of Th1 cells, while significantly increasing the proportion of Treg and Th17 cells. The introduction of both into PD-L1 vaccine could promote 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.
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Keywords:
- PD-L1 /
- vaccine /
- 3-nitrotyrosine /
- 4-nitrophenylalanine /
- T cell differentiation
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