【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。更多还原

【Abstract】 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.更多还原