论文部分内容阅读
目的 研究O 糖基化 (Glycosylation)修饰对HBVPre S( 2 ) 上CTL表位结构及其免疫学活性的影响。方法 选择HBVPre S( 2 ) 上公认的HLA A2限制性CTL表位 44～ 5 3(SILSKTGDPV) ,以Ser44为糖基化位点 ,进行计算机分子模建 ,并利用糖肽合成技术 ,固相合成α GalNAc糖基化CTL表位 ,免疫BALB/c(H 2Db)小鼠 ,观察其诱导CTL活性。结果 α GalNAc 糖基化可改变表位形态使之更适宜与HLA A2类分子结合 ,糖基部分基团可从HLA A2结合沟中向外伸出。与对照组比Ser44α D GalNAcO 糖基化 44～ 5 3肽 ,诱导出较强的针对经抗原预刺激P815细胞的CTL应答 ,特别是 5 0 μg和 5 0 0 μg组 ,而且有明显的剂量 效应关系。 结论 Ser44α D GalNAc 糖基化修饰能改变Pre S( 2 ) 上CTL表位 44～ 5 3的结构 ,并促进特异性CTL应答 ,表明表位糖基化修饰可以调节CTL应答
Objective To investigate the effect of O-glycosylation on the CTL epitope structure and immunological activity of HBV Pre S (2). Methods HLA-A2-restricted CTL epitopes 44-53 (SILSKTGDPV) recognized on HBV Pre S (2) were selected and Ser44 was used as a glycosylation site for computer molecular modeling. Glycopeptide synthesis technology and solid-phase synthesis α GalNAc glycosylated CTL epitopes, BALB / c (H 2Db) mice were immunized to observe its induction of CTL activity. As a result, α GalNAc glycosylation changes the epitope morphology to make it more suitable for binding to HLA class A2 molecules, and the glycosyl moiety can protrude outward from the HLA A2 binding groove. Compared with the control group, Ser44αD GalNAcO glycosylated 44-53 peptides, and induced stronger CTL responses against P815 cells pre-stimulated by antigen, especially in the 50 μg and 500 μg groups, with significant dose-effect relationship. Conclusion Glycosylation of Ser44α D GalNAc can change the structure of CTL epitopes 44-53 on Pre S (2) and promote specific CTL responses, indicating that epitope glycosylation can modulate CTL responses