摘要
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 explore the HLA A2 subtype distribution among Beijing Chinese and its effect on CTL response in vitro to p53 protein based synthetic peptides loaded on dendritic cells. Methods The distribution of HLA A2 genotype and subtypes were analyzed with PCR SSP.The p53 149 157 , p53 264 272 ,and HBVc 18 27 which had high affinity with HLA A201 molecule, were loaded individually on human umbilical cord blood dendritic cells cultured with GM CSF+IL 4 to induce specific CTLs. Results There were 53 cases of HLA A2 genotype among 200 healthy Beijing Chinese , HLA A201 and A207 were the two major subtypes. Dendritic cells (DC), cultured with GM CSF+IL 4, showed enhanced HLA Ⅰ and HLA Ⅱ molecules expression following subsequent addition of TNF α.HLA A201 restricted CTL responses specific to all the studied peptides were readily induced from autologous PBMC by peptide loaded to the DCs. However, HLA A207 restricted CTL response could only be induced by repeatedly using peptide p53 264 272 .Conclusions The distribution profile of HLA A2 subtypes among Beijing Chinese is relatively unique. DC obtained from human cord blood could be used as an effective adjuvant of peptides to overcome the self tolerance to p53 to induce specific CTL responses. Change of one amino acid in the peptide binding region of A2 molecule might significantly influence the antigen presenting ability of certain peptides.
出处
《中华微生物学和免疫学杂志》
CAS
CSCD
北大核心
1999年第1期47-50,共4页
Chinese Journal of Microbiology and Immunology
