摘要
目的我们前期研究显示,无论在汉族人群还是黎族人群中,HLA-DRB1^(*)11∶01均是与机体自发清除HCV相关联的HLA-Ⅱ类基因,因此,本研究的目的是探讨HLA-DRB1^(*)11∶01基因与HCV感染的病毒选择压力及与CD4+T细胞表位的关系。方法对广东地区常见的HCV 6a慢性感染者HLA-DRB1^(*)11∶01阳性组和阴性组的E1E2和NS3基因进行病毒选择压力以及病毒群体扩张的分析。采用覆盖我国常见HCV基因型保守区的CD4+T细胞表位的重叠肽段刺激HCV自发清除组和慢性感染组,通过ELISPT实验,根据每孔的斑点形成细胞数以及在不同组出现的频次评估HLA-DRB1^(*)11∶01基因与CD4+T细胞表位的关系。结果广东地区常见的HCV 6a感染者HLA-DRB1^(*)11∶01阴性组E1E2和NS3的阳性选择位点以及位于CD4+T细胞表位的位点数均大于HLA-DRB1^(*)11∶01阳性组;两组HCV 6a感染者在广东地区均具有群体扩张趋势,且HLA-DRB1^(*)11∶01阴性组的扩张趋势明显高于HLA-DRB1^(*)11∶01阳性组。HCV自发清除组对其中5条肽段(C-52 E2691-707、C-119 NS31545-1560、C-134 NS4A1669-1684、C-154 NS4B1912-1927和C-159 NS4B1929-1944)刺激的应答率较高,HCV慢性感染组对其中的2条肽段(C-111 NS31497-1512和C-130 NS31650-1665)刺激的应答率较高。当考虑HLA-DRB1^(*)11∶01分型时,在慢性感染组和自发清除组HLA-DRB1^(*)11∶01阳性和HLA-DRB1^(*)11∶01阴性PBMCs产生的HCV特异性免疫应答均无统计学差异。结论研究揭示了HLA-Ⅱ类基因HLA-DRB1^(*)11∶01与HCV感染的病毒选择压力及与CD4+T细胞表位的关系,同时,获得HCV泛基因型CD4+T细胞抗原候选表位,为研发适合HCV泛基因型的T细胞疫苗提供基础数据。
Objective HLA-DRB1^(*)11∶01,as a class HLA-Ⅱgene,was reported to be associated with spontaneous clearance of HCV in Han and Li population.Our study was to investigate the effects of viral selection pressure and CD4+T cell epitope on the natural outcome of HCV infection in HLA-DRB1^(*)11∶01 positive infected patients.Methods The positive selection sites and population growth of E1E2 and NS3 genes of common HCV 6a in HLA-DRB1^(*)11∶01 positive and negative groups in Guangdong were respectively analyzed.The peptide library covering the conserved regions of common HCV genotypes was used to stimulate HCV spontaneous clearance group and chronic infection group using ELISPOT method.Reactive peptides were obtained according to the number of spot-forming cells per well and the frequency of occurrence in different groups.Results The positive selection sites(PSSs)of E1E2 and NS3 of common HCV 6a in HLA-DRB1^(*)11∶01 negative group were greater than those in HLA-DRB1^(*)11∶01 positive group.Furthermore,the number of PPSs in CD4+T cell peptide in HLA-DRB1^(*)11∶01 negative group were also greater than those in HLA-DRB1^(*)11∶01 positive group;Both groups of HCV 6a had a population growth in Guangdong,and the expansion trend of HLA-DRB1^(*)11∶01 negative group was significantly higher than that of HLA-DRB1^(*)11∶01 positive group.Compared to HCV chronic infection group,the response rate of HCV spontaneous clearance group to five peptides(C-52 E2_(691-707),C-119 NS3_(1545-1560),C-134 NS4A_(1669-1684),C-154 NS4B_(1912-1927),C-159 NS4B_(1929-1944))was higher.However,the HCV chronic infection group showed a higher response rate to two of the peptides(C-111 NS3_(1497-1512),C-130 NS3_(1650-1665)).When HLA-DRB1^(*)11∶01 typing was considered,there was no significant difference in HCV-specific immune response generated by PBMCs between HLA-DRB1^(*)11∶01 positive and HLA-DRB1^(*)11∶01 negative groups.Conclusion This study revealed the relationship between viral selection pressure of HLA-DRB1^(*)11∶01 HCV infected persons and CD4+T cell antigen epitopes.At the same time,CD4+T cell antigen epitopes of HCV pan-genotype were obtained,providing basic data for the development of T cell vaccine suitable for HCV pan-genotype.
作者
许茹
黄杰庭
王敏
廖峭
单振刚
钟惠珊
戎霞
付涌水
XU Ru;HUANG Jieting;WANG Min;LIAO Qiao;SHAN Zhengang;ZHONG Huishan;RONG Xia;FU Yongshui(Guangzhou Blood Center,Guangzhou 510095,China;The Key Laboratory of Blood Safety in Guangzhou)
出处
《中国输血杂志》
CAS
2023年第7期571-577,共7页
Chinese Journal of Blood Transfusion
基金
国家自然科学基金(32000666)
广州市基础与应用基础研究项目(202201010795)
广州市科技计划项目(2023A03J1000、2023A03J0552)
广州市医学重点学科(2021-2023)项目。
