摘要
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 。
Objective To investigate the effect of modifying O glycosylation on the construction and immunological activity of cytotoxic T lymphocyte (CTL) epitope of HBV Pre S (2) . Methods Based on HBV Pre S (2) (44～53, SILSKTGDPV,HLA A2 restricted) α GalNAc glycosylated viral CTL epitope peptide sequence was built with computer; This glycosylated decapeptide were synthesized and then used to investigate their immunological activity by Balb/c(H 2D b) mice immunization. Results By the model building of HLA A2 and the glycosylated or unglycosylated decamer peptide complex, it was found that monosaccharide glycosylation could change the conformation of decapeptide. Ser44α GalNAc glycosylation, increase the binding affinity and stability by hydrogen bonds and the saccharide could stretch to the outside of the HLA A2 binding groove and might interact to TCR. After mice immunization, the results demonstrated that glycosylated decapeptide could prime stronger specific cytolysis in a dosage dependent manner. Conclusion Ser44α GalNAc glycosylation modification could change the construction of CTL epitope peptide sequence based on HBV Pre S (2) (44～53, SILSKTGDPV,HLA A2 restricted), and facilitate the specific cytolysis. It is demonstrated that glycosylation could regulate the CTL response.
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2000年第10期961-964,共4页
Journal of Third Military Medical University
基金
国家自然科学基金资助项目 !(397890 1 0 )
