山东医药2016，Vol.56Issue(26)：1-5,5.DOI:10.3969/j.issn.1002-266X.2016.26.001
Eps8抗原改造表位 HLA-A*0201限制性抗肿瘤能力观察
Observation on anti-cancer abiIity of HLA-A*0201 -restricted modified epitope from Eps8 antigen
摘要
Abstract
Objective To observe whether modified epitopes from the human epidermal growth factor receptor pathway substrate 8 (Eps8)antigen have leucocyte antigen (HLA -A)*0201 restrictive anti-tumor ability.Methods We obtained the modified peptides from Eps8 containing HLA-A*0201-binding anchor motifs by replacing anchor residues,then we se-lected stable binding affinity peptides E1-9V (ILDDIEFFV)and E1-1Y9V(YLDDIEFFV)by using different computer al-gorithms such as BIMAS,SYFPEITHI database and Aotodock 4.2 software to predict the modified peptides and their bind-ing affinity to HLA-A*0201,respectively.T2 binding assay were performed to verify modified epitopes'binding affinity to HLA-A*0201.Cytotoxic T lymphocytes (CTLs)were induced from peripheral blood mononuclear cells (PBMCs)of HLA-A*0201 positive healthy donors stimulated by modified epitopes E1-9V and E1-1Y9V.The kill rates on SW480, U251,K562,IM-9 and T2 cells were compared between E1-9V and E1-1Y9V peptide-specific CTLs,and meanwhile,the kill rates on T2 cells were compared among E1,E1-9V and E1-1Y9VE1-9V peptide-specific CTLs.Results Both E1-9V and E1-1Y9V formed stable hydrogen bonds with amino acids of HLA-A*0201 molecular B,F docking pockets.T2 binding assay showed that E1-9V and E1-1Y9V showed significantly higher affinity for HLA-A*0201 than the native peptide E1 (all P <0.05).Modified peptide-specific CTLs of E1-9V and E1-1Y9V had lower kill rates on MCF-7 /shRNA and MCF-7 /A2Ab cells than that of MCF-7 cells (all P <0.05).In addition ,the CTLs expressed higher cytotoxicity against tumor cells SW480 and U251 than that of K562 and IM-9 (all P <0.05).E1-1Y9V peptide-specific CTLs showed higher cytotox-icity against tumor cells T2 than E1 and E1-9V peptide-specific CTLs (all P <0.05).Conclusion Compared with native peptide E1,modified epitopes E1-9V and E1-1Y9V have higher binding affinity with HLA-A*0201 and retain immunoge-necity.In addition,the anti-tumor immunity effect of modified epitope E1-1Y9V is stronger than native peptide E1.关键词
表皮生长因子受体通路底物8/抗原改造改造表位/细胞毒性T淋巴细胞/肿瘤疫苗/人白细胞抗原A*0201Key words
epidermal growth factor receptor pathway substrate No.8 (Eps8)/modified epitope/cytotoxic T lympho-cytes/tumor vaccine/human leukocyte antigen A (HLA-A)*0201分类
医药卫生引用本文复制引用
姜春俊,周炜均,谢晓灵,杜静文,张宏毫,贺艳杰,李玉华..Eps8抗原改造表位 HLA-A*0201限制性抗肿瘤能力观察[J].山东医药,2016,56(26):1-5,5.基金项目
国家自然科学基金面上项目（81372249）；国家自然科学基金青年项目（81300431）；广东省中国科学院全面战略合作专项基金资助项目（2013B091500072）；广东省高等教育“创新强校工程”专项基金资助项目（2014GKXM029）。 （）
