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目的对人类白细胞抗原A2分子(HLA-A2)限制性细胞毒性T淋巴细胞(CTL)表位HPV18E77-15进行氨基酸置换修饰,并探讨修饰后多肽的免疫原性。方法根据量化模体方案,比较置换后的多肽与HLA-A2分子的结合系数,采用标准Fmoc方案合成并纯化多肽、细胞毒实验(51Cr释放法),观察多肽是否能够诱导特异性CTLs。结果修饰肽TLQDIVLHV符合HLA-A2分子限制性细胞毒性T细胞的表位要求,具有特异性细胞毒性T细胞诱导活性。结论修饰肽TLQDIVLHV具有更好的结合力和较强的抗原性,可以作为高危型人乳头瘤病毒(HPV)感染治疗性肽疫苗分子设计的候选表位。
Objective To perform amino acid substitution modification on human leukocyte antigen A2 (HLA-A2) restricted cytotoxic T lymphocyte (CTL) epitope HPV18E77-15 and investigate the immunogenicity of the modified peptide. Methods According to the quantification motif protocol, the binding coefficients between the peptides and HLA-A2 molecules were compared. The standard Fmoc protocol was used to synthesize and purify the peptides. The cytotoxicity assay (51Cr release assay) was used to detect whether the peptides could induce specific CTLs. Results The modified peptide TLQDIVLHV conformed to the epitope requirement of HLA-A2 restricted cytotoxic T cells and had specific cytotoxic T cell-inducing activity. Conclusion The modified peptide TLQDIVLHV has better binding ability and stronger antigenicity, and can be used as a candidate epitope for molecular design of therapeutic peptide vaccine for high-risk human papillomavirus (HPV) infection.