基于HBV核心抗原CTL表位的治疗性多肽在体诱导抗原特异性细胞免疫应答的研究

Therapeutic peptides based on CTL epitopes of HBV nucleocapsid induce CTL-mediated cell response in mice

目的 探讨基于表位的治疗性多肽抗原组分、结构与诱导免疫应答之间的关系。方法 用分子设计的理论和方法 ,设计基于HBV抗原免疫优势性CTL、Th及B细胞表位的 3种治疗性多肽候选疫苗分子 ,经Merrifield固相多肽合成技术合成 ,并经HPLC纯化、鉴定。以BALB c(H 2 d)纯系小鼠为实验对象 ,进行体内免疫学功能研究。结果 所设计治疗性多肽分子可在体诱导较强的抗原特异性CTL应答和适度的抗体反应。Th、B细胞表位的引入可增强CTL表位肽的效应。结论 提示在治疗性表位多肽疫苗的分子设计中 ,引入B -、Th表位可显著提高CTL表位肽的免疫原性。

Objective To explore the components and structure of the synthesized therapeutic peptide and how it triggering MHC Ⅰ restricted cytotoxic T cells in vivo Methods A new panel of therapeutic peptides consisting of immunodominant B , T helper and CTL epitopes of HBV Pre S2 region and HBcAg was designed and synthesized, and their immunological properties were investigated in BALB/c(H 2 d)mice Results The synthesized peptides triggered vigorous HBV-specific CTL responses and induced moderate antibody responses specifically and effectively Conclusion The results suggest that rearrangements and combinations of a set of B , T helper and CTL epitopes can lead effective CTL responses in vivo, and that B and T helper epitopes can assist the function of CTL epitope peptides