甲型流感病毒T细胞表位预测及HLA-A2限制性抗原肽筛选  

Prediction of T cell epitopes of influenza A virus and screening of HLA-A2-restricted antigenic peptides

作　　者：韩雪 寸怡娜[1] 朱兰芳 王泯驿 卢天畅 姚宇峰[1] 史荔[1] 陶玉芬[1] HAN Xue;CUN Yina;ZHU Lanfang;WANG Minyi;LU Tianchang;YAO Yufeng;SHI Li;TAO Yufen(Institute of Medical Biology,Chinese Academy of Medical Sciences&Peking Union Medical College,Kunming 650118,Yunnan,China)

机构地区：[1]中国医学科学院&北京协和医学院医学生物学研究所,云南昆明650118

出　　处：《贵州医科大学学报》2022年第5期530-535,541,共7页Journal of Guizhou Medical University

基　　金：云南省科技厅(202002AA100009);中国医学科学院创新计划(2020-I2M-2-014)。

摘　　要：目的通过免疫信息学技术对人类白细胞抗原(HLA)限制性甲型流感病毒T细胞表位进行预测,以期获得通用流感疫苗候选抗原肽。方法以A/California/7/2009(H1N1)为原始毒株,选取流感病毒保守的蛋白聚合酶复合物1(PB1)、核内部蛋白(NP)和基质蛋白1(M1)蛋白,通过免疫表位数据库(IEDB)进行HLA限制性流感病毒T细胞表位的预测、簇分析和人群覆盖率分析,将筛选出的HLA-A*02∶01限制性抗原肽进行HLA-A*02∶01结合的亲和力及稳定性验证。结果共获得甲型流感病毒T细胞表位208个,包括75个PB1表位、78个NP表位及55个M1表位,达到95%以上的全球人群覆盖率;获得HLA-A*02∶01限制性抗原肽6条,可覆盖全球76.98%的人群;新发现HLA-A*02∶01限制性抗原肽PB1-395(LLIDGTASL),其对HLA-A*02∶01分子的亲和力和稳定性均优于其他抗原肽,抗原肽PB1-39的亲和性高于M1-58(P<0.0001)。结论PB1-395(LLIDGTASL)对HLA-A*02∶01分子具有较高的亲和力及稳定性,可作为通用流感疫苗候选抗原肽。Objective To obtain the candidate antigen peptides for universal influenza vaccine through predicting human leukocyte antigen(HLA)-restricted T cell epitopes of influenza A virus by immunoinformatics technology.Methods Using A/California/7/2009(H1N1)as the original strain,conserved protein polymerase complex 1(PB1),nuclear internal protein(NP)and matrix protein 1(M1)proteins of influenza virus were selected.Immune Epitope Database(IEDB)was performed to predict,analyze clusters and population coverage of influenza A virus HLA-restricted T cell epitopes.The binding affinity and stability of screened HLA-A*02∶01-restricted antigen peptides to HLA-A*02∶01 were assayed for verification.Results A total of 208 influenza A virus T cell epitopes were obtained,including 75 PB1 epitopes,78 NP epitopes,and 55 M1 epitopes,reaching a global population coverage rate over 95%.The affinity and stability of newly identified HLA-A*02∶01-restricted antigenic peptide PB1-395(LLIDGTASL)were superior to other antigenic peptides,and the affinity of antigenic peptide PB1-39 was higher than that of M1-58(P<0.0001).Conclusion PB1-395(LLIDGTASL)has high affinity and stability to HLA-A*02∶01 and can be used as a candidate antigen peptide for universal influenza vaccine.

关 键 词：甲型流感病毒 T细胞表位 HLA-A*02∶01 免疫信息学 

分 类 号：R34-33[医药卫生—基础医学]