摘要
目的采用氨基酸置换对人乳头状瘤病毒16型E7抗原的人白细胞抗原A2分子限制性细胞毒性T细胞表位HPV-16E7_(11-20)进行修饰和鉴定。方法运用量化模体方案对置换后的多肽与人白细胞抗原A2分子的结合系数进行比较,以分子模拟方法确定合成序列,采用标准Fmoc方案进行合成与纯化多肽以及标准^(51)Cr释放试验检测特异性细胞毒性T细胞诱导活性。结果修饰多肽符合人白细胞抗原A2分子限制性细胞毒性T细胞的表位要求,十肽YLLDLQPEVT具有特异性细胞毒性T细胞诱导活性。结论修饰表位YLLDLQPEVT具有更好的结合力和较强的抗原性,可以代替原有序列E7_(11-20)(YMLDLQPETT)作为人乳头状瘤病毒感染治疗性肽疫苗分子设计的新表位。
Objective To identify novel epitopes by modification of amino acid substitution of HLA-A2- restricted CTL epitope HPV-16E7 11-20. Methods Quantitative method was used to evaluate the affinity of substitated peptides. To determine the peptide candidates to be synthesized and identified, the molecular models of CTL epitope candidates bound to the HLA-A2 molecule and of the HLA-A2-peptide complex were established by computer molecular modeling. Pepfides were synthesized and purified with standard Fmoc assay. The standard ^51Cr release assay was used to demonstrate their capability of inducing the generation of specific CTL. Results Pepfides modified met the condition of HLA-A2-restricted CTL epitopes. Peptide YLLDLQPEVT had the capability of indueing the generation of specific CTL. Conclusion The modified peptide YLLDLQPEVT had the higher affinity HLA- A2 and antigenicity compared with HPV-16E7 11-20 - So peptide YLLDLQPEVT could be one of the novel HLA-A2- restricted epitopes, as an alternative of HPV-16E7 11-20, for peptide vaccine in HPV infection treatment.
出处
《中华微生物学和免疫学杂志》
CAS
CSCD
北大核心
2006年第11期990-993,共4页
Chinese Journal of Microbiology and Immunology
基金
国家自然科学基金(30500537
30070698)