乙型肝炎病毒抗原表位模拟多肽诱导CTL应答的研究(英文)

Therapeutic peptides based on HBcAg_(18-27) epitope can induce CT L response in vitro and in vivo

目的 应用分子设计技术设计治疗性多肽 ,以探讨基于乙型肝炎病毒 (HepatitisBvirus,HBV)核心抗原优势细胞毒性T淋巴细胞 (CytotoxicTlymphocyts,CTL)表位的多肽设计与启动HLA Ⅰ限制性HBV特异性CD8+ T细胞应答的关系。方法 合成含HBcAg免疫优势CTL表位、Pre S2蛋白优势B细胞表位和破伤风类毒素通用TH 表位的多肽 ,并进行HLA A2 + 人PBMC体外和Balb/c小鼠体内免疫学功能研究。结果 上述多肽可在体内外诱导CD8+ CTL应答。以棕榈酸为分子内佐剂的Palm p4 4可诱导较强的CD8+ CTL应答 ,与单纯多肽比较不需另加佐剂。结论 脂类分子内佐剂可显著提高多肽的免疫原性 ;Palm p4 4可作为乙型肝炎治疗性多肽疫苗设计较有效的候选分子。

Objective To design by computerized molecular des ign methods therapeutic polypeptides against chronic hepatitis B infection to ex plore how to trigger HLA Ⅰrestricted HBV specific CD8 + T cell response and h ence eradicate viruses within hepatocytes. Methods A new panel of polypeptides comprised of the immunodominant CTL and B ep itopes of HBV core antigen(HBcAg) and Pre S2 protein, and the tetanus toxoid T helper epitope were synthesized,and their immunological properties were inve stigated in HLA A2 + human peri pheral blood mononuclear cells(PBMCs)and in Bal b/c mice.Results The results demonstrated that p olypeptides consist of the three kinds of epitopes could evoke in human PBMCs an d in mice CD8 + CTL response. Palm p44,a polypeptide which covalently linked p almitic acids to the carboxyl termini of the potent HBcAg CTL epitope as built in adjuvant induced vigorous CD8 + CTL response, no additional adjuvants were necessary in comparison to the free CTL epitope which failed to induce cell med iated immunity in mice. Conclusions The findings indicate that the lipidic built in adjuvant can efficiently improve the immuno genicity of peptide antigens, and Palm p44 might be a promising candidate for t herapeutic peptide vaccines against chronic viral hepatitis B infection.