论文部分内容阅读
目的研究北方汉族人群中ＨＬＡ－Ａ２亚型的分布及树突状细胞提呈基于ｐ５３基因合成肽体外诱导特异性Ｔ杀伤细胞（ＣＴＬ）反应的影响。方法利用ＰＣＲ－ＳＳＰ技术分析北方汉族人群中ＨＬＡ－Ａ２基因型及其亚型的分布，并在适当Ａ２亚型背景下，选择与ＨＬＡ－Ａ２０１分子具有高亲和性的２个来自ｐ５３蛋白及１个来自ＨＢＶ核心抗原的蛋白合成多肽，将其分别负载到经体外ＧＭ－ＣＳＦ＋ＩＬ－４刺激增殖的人脐带血树突状细胞（ＤＣ）上，诱导自身外周血单个核细胞（ＰＢＭＣ）多肽特异性ＣＴＬ反应。结果２００例北京正常个体中共有５３例ＨＬＡ－Ａ２型，其中以Ａ２０１及Ａ２０７亚型分布最多，亚型分布较分散；在ＧＭ－ＣＳＦ＋ＩＬ－４刺激下获得的典型ＤＣ培养后期加入ＴＮＦ－α，可增加其ＨＬＡ－Ⅰ类及Ⅱ类分子的表达；多肽ｐ５３１４９～１５７，ｐ５３２６４～２７２，ＨＢＶｃ１８～２７均可诱导出ＨＬＡ－Ａ２０１分子限制的自身ＰＢＭＣ肽特异性的ＣＴＬ，然而，只有ｐ５３２６４～２７２经多次刺激才诱导出ＨＬＡ－Ａ２０７分子限制的肽特异性ＣＴＬ。结论北京人群ＨＬＡ－Ａ２基因型分布具有独特性；从人脐带血获得的ＤＣ肽疫苗可以使自身ｐ５３蛋白多肽抗原打破机体的外周耐受状态?
Objective To investigate the distribution of HLA-A2 subtypes in northern Chinese Han population and the effect of dendritic cells on the induction of specific T killer (CTL) responses in vitro from p53-derived synthetic peptides. Methods The distribution of HLA-A2 genotypes and their subtypes in Han population of northern China were analyzed by PCR-SSP technique. Two wild-type p53 proteins from the p53 subtype with high affinity to HLA-A201 One protein synthesized from HBV core antigen was loaded onto human umbilical cord blood dendritic cells (DCs) stimulated by GM-CSF + IL-4 in vitro to induce the specificity of its own peripheral blood mononuclear cells (PBMCs) Sexual CTL response. Results A total of 53 cases of HLA-A2 were found in 200 normal subjects in Beijing. Among them, A201 and A207 subtypes had the most distribution and subtype distribution. In the typical DCs stimulated by GM-CSF + IL-4, Can increase the expression of HLA class I and class II molecules. The polypeptides CT149-157, p53264-272 and HBVc18-27 can induce CTLs specific to their own PBMCs restricted by HLA-A201 molecules. However, only p53264-272 After multiple stimuli, HLA-A207 molecule-restricted peptide-specific CTLs were induced. Conclusion The distribution of HLA-A2 genotypes in Beijing is unique. DC peptide vaccine derived from human umbilical cord blood can make its own p53 protein polypeptide break the peripheral tolerance of the body.