MART-1特异性治疗性多肽诱导CD8+ T细胞应答的研究

目的探讨基于黑色素瘤特异性抗原MART-127-35表位的治疗性多肽抗原组分、结构,及诱导抗原特异性CD8+ T细胞应答的关系.方法用蛋白质分子设计技术,设计基于黑色素瘤特异性抗原MART-127-35表位、HIV Tat49-57CCP序列及破伤风类毒素通用Th表位的治疗性多肽候选分子,经Merrifield固相多肽合成技术合成,HPLC纯化、鉴定.以黑色素瘤病人PBMC为实验对象,对其诱导T细胞增殖、Th1极化、抗原特异性CD8+ CTL效应进行研究.结果所设计治疗性多肽分子可在体外诱导Th1极化和抗原特异性CD8+T细胞应答,含Th、CTL表位的双表位肽抗原略优于单纯CTL表位肽,含Th、CTL表位和HIV Tat49-57CCP序列的肽抗原效应显著优于前二者(P<0.05).结论提示基于黑色素瘤特异性抗原优势CTL表位、HIV Tat49-57CCP序列及破伤风类毒素通用Th表位的治疗性多肽设计可显著提高肿瘤治疗性小分子肽的免疫原性.

Therapeutic peptide based on CTL epitope of human melanoma antigen MART-1 can induce CD8+ T cell response in vitro

Objective To explore how to improve the immunogenicity of short epitope peptides of triggering melanoma MART 1 specific CD8 +T cell responses Methods Therapeutic peptides based on the immunodominant MART 127 35, HIV Tat49 57CCP sequence and a tetanus toxoid universal Th epitope were designed and synthesized The immunological functions were studied in PBMCs from HLA A2 + melanoma patients Results The results demonstrated that the peptides could trigger vigorous MART 1 specific CD8 + CTL activities in vitro The function of peptide containing MART 127 35 and tetanus universal Th epitope was more vigorous than that of MART 127 35 peptide, and the immunogenicty of the peptides with HIV Tat49 57CCP sequence, MART 127 35 and tetanus universal Th epitope was the most vigorous Conclusion Linkage of HIV Tat49 57CCP sequence and a tetanus universal Th epitope could dramatically improve the immunogenictiy of the MART 127 35 epitope peptide