小鼠MHC-Ⅰ/MHC-Ⅱ类分子限制性表位MAGE-3多肽疫苗的设计及其免疫效应  

Identification and Immune response of Murine MAGE-3 Derived MHC-Ⅰ/ MHC-Ⅱ Restricted Peptide Epitope

作　　者：李志花[1] 杨君[1] 周嘉嘉[1] 陈汝福[1] 

机构地区：[1]中山大学孙逸仙纪念医院肿瘤科,广东广州510120

出　　处：《中山大学学报（医学科学版）》2010年第1期138-140,共3页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：国家自然科学基金(30872485);国家高科技计划(863)项目(2007AA02Z437);广州市科技计划项目(2007Z3-D2061)

摘　　要：【目的】设计小鼠MHC-I/MHC-II类分子限制性表位黑色素瘤抗原-3(MAGE-3)多肽疫苗即包含CD4+-CD8+T细胞表位的MAGE-3多肽抗原,并探讨其免疫效应。【方法】采用计算机模拟设计的方法,结合文献资料选择MHC-I/MHC-II类分子限制性表位的MAGE-3多肽。采用酶联免疫斑点实验(ELISPOT)、细胞毒性实验评价多肽诱导T淋巴细胞的增殖能力及刺激的T淋巴细胞释放细胞因子的能力。【结果】获得的联合表位多肽序列为FITC-YEEYYPLIFLDNDQETMETSEEEEYEEYYPLIF,高效液相色谱法分析多肽纯度≥90%。MAGE-3表位多肽抗原能够诱导T淋巴细胞增殖,并诱导T淋巴细胞分泌IFN-γ,高于对照组(49vs.6spots/106,P≤0.05)。MAGE-3表位多肽可诱导细胞毒T淋巴细胞使42%的MFC细胞溶解破裂,高于对照组(P≤0.05)。【结论】包含CD4+-CD8+T细胞表位的MAGE-3多肽抗原在体外实验中显示有一定的免疫效应,此抗原肽可作为多肽疫苗用于对表达MAGE-3抗原的H-2KK型小鼠胃癌进行免疫治疗。【Objective】 To design murine MAGE-3 derived MHC-I / MHC-II restricted peptide epitope,which containing CD4＋-CD8＋ T cell epitope peptides antigen.【Methods】 The epitope peptides were made through computer simulation designing,and peptide epitopes qualification tests were performed after the synthesis of peptide antigen,ELISPOT and cell-toxic analysis were used to evaluate the proliferation ability and cytokine-release ability of peptide-stimulated T cell.【Results 】 The sequence of obtained MAGE-3 derived restricted epitope peptide was FITC-YEEYYPLIFLDNDQETMETSEEEEYEEYYPLIF,of which the purity ≥ 90% tested by high performance liquid chromatography.MAGE-3 epitope peptide antigen could induce T lymphocyte proliferation,and induce T lymphocyte to secret IFN-γ,which higher than that of the control group （49 vs.6 spots / 106,P ≤ 0.05）.MAGE-3 epitope peptide could induce cytotoxic T lymphocytes to cause 42% of MFC cell lysis rupture,higher than control group （P ≤ 0.05）.【Conclusion】 CD4＋-CD8＋ T cell epitope MAGE-3 peptide antigen showed considerable immunological effect in vitro,and such a peptide antigen can work as therapeutic polypeptide vaccine for H-2KK mice gastric cancer which express MAGE-3 antigen.

关 键 词：MAGE-3 抗原表位 T淋巴细胞 免疫 

分 类 号：R3[医药卫生—基础医学]