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幽门螺杆菌黏附素HLA-DRB1限制性CD4+T细胞表位的预测与鉴定 被引量：1

Identification of HLA-DRB1 restricted CD4^+ T-cell epitopes from HpaA of Helicobacter pylori
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摘要 目的针对中国汉族高频HLA-DRB1基因型人群,预测与鉴定幽门螺杆菌(Helicobacter pylori,H.pylori)黏附素蛋白A亚单位(neuraminyllactose-binding hemagglutinin,HpaA)CD4+T细胞表位。方法通过Allele Frequency Net数据库分析中国汉族人群HLA-DRB1高频基因型,利用NetMHCIIpan对HpaA蛋白中能被这些高频基因型递呈的CD4+T细胞表位进行预测;通过PCR-SBT法筛选携带有这些高频基因型的H.pylori感染者,利用重组HpaA抗原刺激感染者外周血单个核细胞体外扩增出HpaA抗原特异性T淋巴细胞后利用合成短肽对所预测表位进行鉴定,通过抗体阻断实验对表位的HLA限制性进行分析,利用DC细胞负载重组HpaA蛋白对表位的自然递呈特征进行分析。结果中国汉族人群中HLA-DRB1高频基因型为DRB1*0901(14.4%)、DRB1*1202(13.3%)和DRB1*1501(10.8%),针对上述3种高频基因型预测出24个HpaA蛋白CD4+T细胞表位。其中,4个表位:HpaA39-53(HLA-DRB1*0901)、HpaA42-56(HLA-DRB1*0901)、HpaA89-103(HLA-DRB1*1202)和HpaA87-101(HLA-DRB1*1501)可有效刺激体外扩增的HpaA特异性T细胞产生高水平IFN-γ,且均能被DC细胞自然递呈。结论鉴定得到的4个HLA-DRB1限制性CD4+T细胞表位有可能成为H.pylori表位疫苗设计的候选抗原。 This study designed to identify the immunodominant CD4＋ T cell epitopes derived from HpaA of Helicobacter pylori （H. pylori） which restricted to the most popular HLA molecules of Chinese Han population. Firstly, The frequencies of HLA-DRB1 alleles of Chinese Han population was analyzed by using Allele Frequency Net data base, and CD4＋ T cell epitopes derived from HpaA protein were predicted by using NetMHCIIpan. Then, H. pylori infected subjects expressing the most popular HLA molecules were identified by PCR-SBT, and HpaA- specific T cell lines expanded in vitro by using the recombinant HpaA protein, and peripheral blood mononuclear ceils of H. pylori infected subjects were used to identify the immunodominant epitopes. Furthermore, HLA blocking assay was used to analyze the HLA restrictions, and DCs pulsed recombinant HpaA protein were used to confirm be natural presenting characteristics of the epitopes. Result showed that the most popular three HLA alleles in Chinese Han population were DRBl＊0901（14.4%）, DRBl＊1202（13.3%） and DRBl＊1501（10.8%）, and 24 epitopes restricted to these three HLA-DRB1 molecules were predicted, in which HLA-DRBl＊0901/HpaA39_53, HLA-DRB 1 ＊ 0901/HpaA42-56, HLA-DRB 1 ＊ 1202/HpaAsg-103 and HLA-DRB 1 ＊ 15 01/HpaA87-101 aroused the strongest HpaA-specific T cells responses of IFN-＋/ production in vitro. And all of the four epitopes could be naturally presented by DCs. In conclusion, these four CD4＋ T cell epitopes identified here might be used as candidate antigens for H. pylori epitope vaccine design.
作者 胡健 郭红 李滨 陈立 何亚非 孙合强 李海波 赵卓 吴超
机构地区 第三军医大学新桥医院消化内科 第三军医大学医学检验系临床微生物及免疫学教研室
出处 《免疫学杂志》 CAS CSCD 北大核心 2014年第2期124-128,132,共6页 Immunological Journal
基金 国家自然科学基金(81072493) 重庆市自然科学基金(2011BB5043) "十一五"国家重大新药创制专项(2009ZX09102-220)
关键词 幽门螺杆菌 CD4+T细胞表位 幽门螺杆菌鞭毛黏附素A亚单位 人白细胞抗原-DRB1 Helicobacter pylori CD4＋T cellepitopes HpaA HLA-DRB1
分类号 R378 [医药卫生—病原生物学]
  • 相关文献

参考文献12

  • 1Wroblewski LE, Peek RM, Wilson KT. Helicobacter pylori and gastric cancer: factors that modulate disease risk[J]. Clin Microbiol Rev, 2010, 23(4): 713-739.
  • 2Malfertheiner P. The intriguing relationship of Helicobacter pylori infection and acid secretion in peptic ulcer disease and gastric cancer[J]. Dig Dis, 2011, 29(5): 459-464.
  • 3Kwon SB, Lee KL, Kim JS, et al. Antibiotics-associated diarrhea and other gastrointestinal abnormal responses regarding Helicobacter pylori eradication] [J]. Korean J Gastroenterol, 2010, 56(4): 229-235.
  • 4Carlsohn E, Nystrom J, Bolin I, et al. HpaA is essential for Helicobacter pylori colonization in mice[J]. Infect Immun, 2006, 74(2): 920-926.
  • 5Robinson J, Waller MJ, Parham P, et al. IMGT/HLA and IMGT/MHC: sequence databases for the study of the major histocompatibility complex [J]. Nucleic Acids Res, 2003, 31(1): 311-314.
  • 6李宁一,陈立,李滨,杨武晨,章金勇,毛旭虎,吴超,邹全明.重庆地区汉族人群HLA-DRB1等位基因多态性研究[J].免疫学杂志,2012,28(4):344-348. 被引量：2
  • 7Ebert LM, Liu YC, Clements CS, et al. A long, naturally presented immunodominant epitope from NY-ESO-1 tumor antigen: implications for cancer vaccine design[J]. Cancer Res, 2009,69(3): 1046-1054.
  • 8Zhang L, Udaka K, Mamitsuka H, et al. Toward more accurate pan-specific MHC-peptide binding prediction: a review of current methods and tools[J]. Brief Bioinform, 2012, 13(3): 350-364.
  • 9Chaves FA, Lee AH, Nayak JL et al. The utility and limitations of current Web-available algorithms to predict peptides recognized by CD4 T cells in response to pathogen infection[J]. J Immunol, 2012, 188(9): 4235-4248.
  • 10Chen L, Li B, Yang WC, et al. A Dominant CD4 (+) T-cell response to Helicobacter pylori reduces risk for gastric disease in humans [J]. Gastroenterology, 2013, 144(3): 591- 600.

二级参考文献14

  • 1王卓敏,杨春隆,林乾飞,孙宽,郭玉琛,冯明亮,嵇月华,张工梁.长春汉族人HLA—ABC及HLA—DR、DQ抗原分布[J].中国输血杂志,1993,6(3):158-159. 被引量：2
  • 2Handunnetthi L,Ramagopalan SV,Ebers GC,et al.Regulationof major histocompatibility complex class II geneexpression,genetic variation and disease[J].Genes Immun,2010,11(2):99-112.
  • 3de Bakker PIW,McVean G,Sabeti PC,et al.A high-resolutionHLA and SNP haplotype map for disease association studies inthe extended human MHC[J].Nat Genet,2006,38(10):1166-1172.
  • 4Robinson J,Waller MJ,Parham P,et al.IMGT/HLA andIMGT/MHC:sequence databases for the study of the majorhistocompatibility complex[J].Nucleic Acids Res,2003,31(1):311-314.
  • 5BrayRA,HurleyCK,Kamani NR,et al.National marrowdonorprogram HLA matching guidelines for unrelated adult donorhematopoietic cell transplants[J].Biol Blood MarrowTransplant,2008,14(9):45-53.
  • 6Deng Z,Deng Z,Wang D,et al.HLA-C polymorphisms andPCR dropout in exons 2 and 3 of the Cw*0706 allele insequence-based typing for unrelated Chinese marrow donors[J].Human Immunology,2010,71(6):577-581.
  • 7Velickovic ZM,Delahunt B,Carter JM.HLA-DRB1 andHLA-DQB1 polymorphisms in Pacific Islands populations[J].Tissue Antigens,2002,59(5):397-406.
  • 8Krokowski M,Bodalski J,Bratek A,et al.HLA class II alleleand haplotype distribution in a population from centralPoland[J].Eur J Immunogenet,1998,25(1):5-9.
  • 9Ravikumar M,Dheenadhayalan V,Rajaram K,et al.Associations of HLA-DRB1,DQB1 and DPB1 alleles withpulmonary tuberculosis in south India[J].Tuber Lung Dis,1999,79(5):309-317.
  • 10Ando T,Ishikawa T,Kato H,et al.Synergistic effect of HLAclass II loci and cytokine gene polymorphisms on the risk ofgastric cancer in Japanese patients with Helicobacter pyloriinfection[J].Int J Cancer,2009,125(11):2595-2602.

共引文献1

同被引文献15

  • 1Douglas JM Jr. Penicillin treatment of syphilis: clearing away the shadow on the land[J]. JAMA, 2009, 301(7): 769- 771.
  • 2Tucker JD, Cohen MS. China's syphilis epidemic: epidemiology, proximate determinants of spread, and control responses[J]. Curr Opin Infect Dis, 20l 1, 24(1): 50- 55.
  • 3Cameron CE, Lukehart SA. Current status of syphilisvaccine development: need, challenges, prospects [J]. Vaccine, 2014, 32(14): 1602-1609.
  • 4Cullen PA, Cameron CE. Progress towards an effective syphilis vaccine: the past, present and future[J]. Expert Rev Vaccines, 2006, 5(1): 67-80.
  • 5Desrosiers DC, Anand A, Luthra A, et al. TP0326, a Treponema pallidum I-barrel assembly machinery A (BamA) orthologue and rare outer membrane protein[J]. Mol Microbiol, 2011, 80(6): 1496-515.
  • 6Cameron CE, Lukehart SA, Castro C, et al. Opsonic potential, protective capacity, and sequence conservation of the Treponema pallidum subspecies pallidum Tp92 [J]. J Infect Dis, 2000, 181(4): 1401-1413.
  • 7Zhao F, Wu Y, Zhang X, et al. Enhanced immune response and protective efficacy of a Treponema pallidum Tp92 DNA vaccine vectored by chitosan nanoparticles and adjuvanted with IL-2[J]. Hum Vaccin, 2011, 7(10): 1083- 1089.
  • 8Pishraft Sabet L, Taheri T, Memarnejadian A, et al. Immunogenicity of multi-epitope DNA and peptide vaccine candidates based on core, E2, NS3 and NS5B HCV epitopes in BALB/c mice[J]. Hepat Mon, 2014, 14(10): e22215.
  • 9Murphy KP, Travers P immunobiology [M]. 74 ed. 2008: 695-696.
  • 10Walpoa M. Janeway" s New York: Garland Science, Cullen PA, Cameron CE. Progress towards an effective syphilis vaccine: the past, present and future[J]. Expert Rev Vaccines, 2006, 5(1): 67-80.

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免疫学杂志
2014年 第2期

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