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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 therapeutic peptides based on molecular design techniques to study the design and initiation of HLA class I-specific HBV-specific CD8 + peptides based on the epitopes of cytotoxic T lymphocytes (CTLs) of the core antigen of HepatitisBvirus (HBV) T cell response to the relationship. Methods The CTL epitopes of HBcAg immunization, preferential B cell epitope of Pre S2 protein and universal TH epitope of tetanus toxoid were synthesized and the immunological function of HLA A2 + human PBMC in vitro and Balb / c mice was studied. Results The above polypeptides induce CD8 + CTL responses in vitro and in vivo. Palm p4 4 with palmitic acid as an intramolecular adjuvant induced a stronger CD8 + CTL response than the simple peptide without adjuvant. Conclusions Lipid intramolecular adjuvant can significantly improve the immunogenicity of peptides. Palm p4 4 can be used as a candidate molecule for the therapeutic peptide vaccine of hepatitis B.