肿瘤抗原MAGE-2多抗原肽疫苗的设计合成及免疫原性研究  

Studies on the molecular design, chemical synthesis, and immunogenicity of multiple antigen peptide vaccines from MAGE-2

作　　者：耿淼[1] 吴玉章[1] 管孝鞠[1] 贾正才[1] 周伟[1] 邹丽云[1] 

机构地区：[1]第三军医大学基础医学部全军免疫学研究所,重庆400038

出　　处：《第三军医大学学报》2004年第15期1330-1332,共3页Journal of Third Military Medical University

基　　金：国家自然科学基金资助项目 ( 30 10 0 16 7) ;国家重点基础研究发展规划资助项目 ("973"项目 ) ( 2 0 0 1CB510 0 0 1)~~

摘　　要：目的　采用多抗原肽 (multipleantigenpeptide ,MAP)设计方案 ,提高线性短肽的免疫原性。方法　对肿瘤抗原MAGE 2 2 2 0 2 2 8细胞毒性T细胞 (cytotoxicTlymphocyte ,CTL)表位进行分子修饰 ,设计、合成四分支多抗原肽 (MAP4)。标准Fmoc合成方案进行合成 ,液相色谱 质谱联用 (LC MS)进行目的肽鉴定。以体外刺激人外周血单核细胞 (PBMC)诱导CTL效应及IFN γ分泌 ,标准 51 Cr释放实验与Elispot实验进行免疫原性的研究。结果　标经准 51 Cr释放实验验证 ,低浓度的MAP4可以诱导出有效的CTL效应 ,Elispot实验显示MAP4能够有效诱导的IFN γ分泌。结论　MAP的构建能够增强CTL效应和IFN γ的分泌 。Objective To improve the immunogenicity of linear peptide by employing the multiple antigen peptide (MAP) as vaccine candidate structure. Methods The molecular engineering experiment of the CTL epitope peptide MAGE 2220 228 was performed. The four branch MAP (MAP4) was synthesized by Fmoc method and the purity was analyzed by RP HPLC. The peptide was identified by liquid chromatography (LC) and mass spectrum (MS). The MAP4 immunogenicity was studied using human peripheral blood mononuclear cells (PBMCs) from HLA A2+ healthy donors. The CTL response and the IFN γ secretion were detected by standard 51 Cr release assay and enzyme linked immunospot (ELISPOT) assay. Results Low concentration MAP4 could induce effective CTL response and generous IFN γsecretion in vitro . Conclusion The MAP structure is a good candidate structure for designing a new generation of peptide based vaccine, which can induce effective CTL response and generous IFN γ secretion. The MAP structure can also improve the immunogenicity of short CTL peptide.

关 键 词：肿瘤抗原MAGE-2 MAP 免疫原性 

分 类 号：R392.7[医药卫生—免疫学] R394.33[医药卫生—基础医学]