肿瘤相关抗原p572肽的修饰及其功能分析  

Modification and Analysis of hTERT Assoiated Peptide p572

作　　者：仇全[1] 李颖[1] 钱关祥[1] 

机构地区：[1]上海第二医科大学生物化学与分子生物学教研室,上海200025

出　　处：《现代免疫学》2004年第6期470-476,共7页Current Immunology

摘　　要：由于大多数肿瘤相关抗原是自身抗原 ,且免疫耐受通常保护个体避免发生自身免疫反应 ,所以用肿瘤相关抗原在体内刺激抗肿瘤T细胞反应时 ,免疫耐受是很难克服的障碍之一。一般认为 ,免疫耐受主要针对肿瘤的一些明显表位 ,而与HLA低亲和力的潜在表位则可能不受免疫耐受的影响。基于这一假设 ,我们设计合成了三条人端粒酶逆转录酶 (hTERT )相关的抗原肽 ,p5 72 (RLFFYRKSV )、pY5 72 (YLFFYRKSV )和pF5 72 (FLFFYRKSV ) ,p5 72是近期研究较多的一条与HLA A2 1分子低亲和力的 9肽 ,pY5 72和pF5 72是我们根据 9肽氨基酸位置特点突变合成 ,理论上它们与HLA A2 1分子的亲和力要高于p5 72 ,用T2细胞模型检测证实了这一点。DC细胞是最强的抗原提呈细胞 ,我们在试验中用DC细胞负载不同的肽在体外刺激特异性CTL的分化。Because most tumor associated antigens(TAA)are self antigens, tolerance that normally protects the individual from the development of autoimmunity stands as a major potential obstacle in the development of T cell responses capable of eradicating tumors in vivo. Since this tolerance primarily concerns dominant epitopes, we hypothesized that targeting cryptic epitopes that have a low affinity for HLA would be an efficient strategy to breach the tolerance to tumor antigens. So we synthesized three hTERT associated peptides:p572(RLFFYRKSV)with low affinity with HLA-A2.1, which is a hot peptide studied recently; another two peptides pY572(YLFFYRKSV)and pF572(FLFFYRKSV)are analogue peptides of p572, which are respectively modified by a single amino acid substitution in position one which theoretically augmented its relative affinity for the HLA-A2.1 molecule. Tested with T2 cell model in vitro, we have confirmed that this. DC is the most efficient antigen presentating cells, and we succeeded in generating specific CTL with DC loaded with different peptides in vitro.

关 键 词：人端粒酶逆转录酶 免疫耐受 表位 树突状细胞 细胞毒淋巴细胞 

分 类 号：R392.12[医药卫生—免疫学]