程序性死亡受体配体-1 B细胞表位预测与分析  

Analysis and predication of B cell epitopes of programmed cell death ligand 1

作　　者：陈旭东[1] 程开[1] 吕开绩 张丽芳[2] 朱冠保[1] 

机构地区：[1]温州医科大学附属第一医院胃肠外科,浙江温州325015 [2]温州医科大学微生物学与免疫学教研室分子病毒与免疫研究所热带医学研究所,浙江温州325035

出　　处：《温州医科大学学报》2018年第1期7-12,19,共7页Journal of Wenzhou Medical University

基　　金：国家自然科学基金资助项目(81372447)

摘　　要：目的:预测和筛选程序性死亡受体配体-1(PD-L1)的B细胞表位,以期用于能够阻断程序性死亡受体(PD-1)和其配体结合的拮抗剂的研究。方法:以人和小鼠的PD-L1的全长氨基酸序列为基础,利用生物信息学方法,采用Hopp&Woods的亲水性方案、Zimmerman极性参数、Jameson-Wolf抗原指数方案和Emini表面可及性方案等,结合PD-L1的二级结构与其柔性区域对PD-L1的优势B细胞表位区段进行综合分析,建立3D模型,结合功能定位,进一步运用抗原指数分析预测,将人与小鼠的B细胞表位进行对比分析,并与多种实验动物进行同源性分析。结果:人和小鼠的PD-L1均为一型跨膜蛋白,均由290个氨基酸残基组成,相对分子质量均为33 kDa。人和小鼠PD-L1的胞外段分别位于N端的19~238和19~239。经综合分析,与PD-1、PDL1结合相关的人和小鼠的B细胞优势表位可能分别位于其氨基酸序列N端的41~46、60~63、71~75和40~48、58~63、72~88区段,即KFPVEK、EDKN、EEDLK和RFPVERELDL、EKEDE、EDLKPQH肽段;同源性分析显示包含本研究所预测的表位的氨基酸序列在多种动物之间高度保守。结论:将生物信息学预测B细胞表位的方法与3D模型建立及功能定位的方法相结合,筛选出人和鼠各3条与PD-L1功能区相近的优势B表位,为阻断PD-1和PD-L1结合的拮抗剂的研究提供了理论基础。Objective： To predict and screen the B-cell epitopes of the programmed cell death ligand 1 （PD-L1）, in the hope of being used in the research of antagonist to block the protein-protein interaction between the transmembrane protein programmed cell death protein 1 （PD-1） and its ligand. Methods： Base on the full-length amino acid sequence of human and mouse PD-L1, the B-cell epitopes of the PD-L1 were predicted by bioinformatics method, including the secondary structure, the hydrophilic plot technique, polarity parameters, surface probability, and the antigenic index. Along with molecular modeling and functional mapping, antigenic index calculation was further taken as a standard to determine target epitopes. The amino acid sequence alignment of the predicted B epitopes of PD-L1 was blasted with other four kinds of experimental animal PD-L1. Results： Human and mouse PD-L1 was a 33 kDa type I membrane protein consisting of 290 amino acids. Extracellular part of human and mouse PD-L1 was at 19-238 and 19-239 respectively. The predicted B-cell epitopes of human and mouse PD-L1＇s which could be used in the research of antagonist to block the protein-protein interaction between PD-1 and PD-L1＇s might exist in N-terminal of amino acid sequence： 41-46 （KFPVEK）, 60-63 （EDKN）, 71-75 （EEDLK） and 40-48 （RFPVERELDL）, 58-63 （EKEDE）, 72-88 （EDLKPQH） respectively. Homology analysis showed the amino acid sequence （41-50, 58-62, 71-80） which contains the predicted B-cell epitopes was highly conservative in different species. Conclusion： Bioinformatic prediction along with molecular modeling and functional mapping which concludes in three amino acid seuences each for human and mouse provides a theoretical basis for further study of antagonist to block the protein-protein interaction between PD-1 and PD-L1.

关 键 词：程序性死亡受体配体-1 B细胞表位 肿瘤 免疫疗法 

分 类 号：R730.51[医药卫生—肿瘤]