Advanced Search
NING Hongyu, JIANG Tao, ZHANG Rui, HE Yu, YAO Wenbing, TIAN Hong. Effects of immunogenic HER2 on the differentiation of T-cell in mouse[J]. Journal of China Pharmaceutical University, 2018, 49(1): 102-108. DOI: 10.11665/j.issn.1000-5048.20180115
Citation: NING Hongyu, JIANG Tao, ZHANG Rui, HE Yu, YAO Wenbing, TIAN Hong. Effects of immunogenic HER2 on the differentiation of T-cell in mouse[J]. Journal of China Pharmaceutical University, 2018, 49(1): 102-108. DOI: 10.11665/j.issn.1000-5048.20180115
shu

Effects of immunogenic HER2 on the differentiation of T-cell in mouse

More Information
    Graphical Abstract
    • Abstract
  • In order to investigate the effects of p-nitrophenylalanine on the differentiation of T lymphocyte, human epidermal growth factor receptor 2(HER2)mutants were constructed by incorporating p-nitrophenylalanine to the extracellular domain of HER2. Mice were immunized with HER2 mutant to analyze the effects of p-nitrophenylalanine on the differentiation of T cell subsets. The results showed that the immunogenicity of HER2 protein was significantly enhanced by incorporation of immunogenic amino acids. HER2 mutants induced production of more anti-WT-HER2 antibody and greater titer of antibody than PBS and wild-type HER2 in the fifth week. The differentiation frequency of Th1 and Th2 cells showed no significant difference, but the differentiation frequency of Tfh cell was found to increase from 4% to 8%, while the differentiation frequency of Treg cell was found to decrease from 5% to 1% through flowcytometry analysis. The gene expression of Bcl-6 and FOXP3 were determined by quantitative real-time PCR. The results showed that the expression of Bcl-6 mRNA increased about 2 fold, while the expression of FOXP3 mRNA could be decreased to about 50% in HER2 mutant-immunized group. The secretion level of IL-21 in serum was also detected to increase from 4 to 28 pg/mL in HER2 mutant-immunized group. The above results confirm that HER2 mutants containing p-nitrophenylalanine can cause an efficient immune response by activating Tfh cell differentiation.
    • FullText(HTML)
    • References (20)
  • [1]
    Gruenewald J,Tsao ML,Perera R,et al.Immunochemical termination of self-tolerance[J].Proc Natl Acad Sci U S A,2008,105(32):11276-11280.
    [2]
    Hardy LL, Wick DA, Webb JR. Conversion of tyrosine to the inflammation-associated analog 3′-nitrotyrosine at either TCR-or MHC-contact positions can profoundly affect recognition of the MHC class I-restricted epitope of lymphocytic choriomeningitis virus glycoprotein 33 by CD8 T cells[J].J Immunol,2008,180(9):5956-5962.
    [3]
    Xie J,Schultz PG.An expanding genetic code[J].Methods,2005,36(3):227-238.
    [4]
    Kessel C,Nandakumar KS,Peters FB,et al.A single functional group substitution in C5a breaks B cell and T cell tolerance and protects against experimental arthritis[J].Arthritis Rheumatol,2014,66(3):610-621.
    [5]
    Hallam TJ, Wold E, Wahl A, et al. Antibody conjugates with unnatural amino acids[J].Mol Pharm,2015,12(6):1848-1862.
    [6]
    Grunewald J,Hunt GS,Dong L,et al.Mechanistic studies of the immunochemical termination of self-tolerance with unnatural amino acids[J].Proc Natl Acad Sci U S A,2009,106(11):4337-4342.
    [7]
    Gauba V, Grunewald J, Gorney V, et al. Loss of CD4 T-cell-dependent tolerance to proteins with modified amino acids[J].Proc Natl Acad Sci U S A,2011,108(31):12821-12826.
    [8]
    Zhang TJ,Tian H,Gao XD.Advances in research on antitumor activities of HER2-based peptide vaccines[J].Prog Pharm Sci(药学进展),2013,37(10):516-521.
    [9]
    Zhang R,Tian H,Gao XD,et al.Application of next generation genome editing technology in gene therapy and biopharmaceuticals[J].J China Pharm Univ(中国药科大学学报),2014,45(4):504-510.
    [10]
    Yao DN,Xu XW,Yu HB,et al.Screening system for amber suppressor tRNA based on inducible high-copynumber plasmid[J].J China Pharm Univ(中国药科大学学报),2013,44(2):174-178.
    [11]
    Chen X,Ma W,Zhang T,et al.Phenotypic Tfh development promoted by CXCR5-controlled re-localization and IL-6 from radiation-resistant cells[J].Protein Cell,2015,6(11):825-832.
    [12]
    Moser B.CXCR5,the defining marker for follicular B helper T(T-FH)cells[J].Front Immunol,2015,6:296.
    [13]
    Mcguire HM,Vogelzang A,Warren J,et al.IL-21 and IL-4 collaborate to shape T-dependent antibody responses[J].J Immunol,2015,195(11):5123-5135.
    [14]
    Choi YS,Yang JA,Yusuf I,et al.Bcl6 expressing follicular helper CD4 T cells are fate committed early and have the capacity to form memory[J].J Immunol,2013,190(8):4014-4026.
    [15]
    Liu X,Yan X,Zhong B,et al.Bcl6 expression specifies the T follicular helper cell program in vivo[J].J Exp Med,2012,209(10):1841-1852.
    [16]
    Ozaki K,Spolski R,Ettinger R,et al.Regulation of B cell differentiation and plasma cell generation by IL-21,a novel inducer of Blimp-1 and Bcl-61[J].J Immunol,2004,173(9):5361-5371.
    [17]
    Crotty S. A brief history of T cell help to B cells[J].Nat Rev Immunol,2015,15(3):185-189.
    [18]
    Toellner KM.Cognate interactions:extrafollicular IL-4 drives germinal-center reactions,a new role for an old cytokine[J].Eur J Immunol,2014,44(7):1917-1920.
    [19]
    Zhang Y,Garcia-Ibanez L,Toellner KM.Regulation of germinal center B-cell differentiation[J].Immunol Rev,2016,270(1):8-19.
    [20]
    Dan JM,Arlehamn CSL,Weiskopf D,et al.A cytokine-independent approach to identify antigen-specific human germinal center T follicular helper cells and rare antigen-specific CD4(+)T cells in blood[J].J Immunol,2016,197(3):983-993.
    • Related Articles

  • Related Articles

    [1]NING Manru, XU Kehui, HANG Taijun, SONG Min. Separation and identification of folic acid and its related substances by liquid chromatography-mass spectrometry[J]. Journal of China Pharmaceutical University, 2025, 56(1): 56-64. DOI: 10.11665/j.issn.1000-5048.2024052201
    [2]XIA Ying, LONG Jiayi, DAI Haoran, SHEN Mengyuan, GUO Hongli, HU Yahui, CHEN Feng. Determination of digoxin in human plasma by LC-MS/MS and its application in pediatric patients[J]. Journal of China Pharmaceutical University, 2021, 52(6): 719-724. DOI: 10.11665/j.issn.1000-5048.20210610
    [3]XIA Ying, GUO Hongli, HU Yahui, CHEN Feng. Therapeutic drug monitoring for monoclonal antibody：progress in the application of LC-MS/MS technique[J]. Journal of China Pharmaceutical University, 2021, 52(1): 122-128. DOI: 10.11665/j.issn.1000-5048.20210117
    [4]NI Yueling, HAN Xing, SONG Min, HANG Taijun. Identification of the related substances of cyclosporin A by LC-MS techniques[J]. Journal of China Pharmaceutical University, 2019, 50(4): 423-437. DOI: 10.11665/j.issn.1000-5048.20190407
    [5]LIANG Fangmei, NI Yueling, WANG Lu, HANG Taijun, SONG Min. Structural identification of the related substances of fusidic acid by LC-MS[J]. Journal of China Pharmaceutical University, 2018, 49(3): 322-332. DOI: 10.11665/j.issn.1000-5048.20180311
    [6]LIU Chaoyi, ZHANG Ge, HANG Taijun, WANG Lei, ZHANG Xiaofei, SONG Min. Identification of related substances in rivaroxaban by LC-MS[J]. Journal of China Pharmaceutical University, 2015, 46(4): 450-457. DOI: 10.11665/j.issn.1000-5048.20150411
    [7]ZHANG Lu, QIANG Shuping, ZHANG Yunjing, WANG Lei, ZHANG Xiaofei, HANG Taijun. Preliminary identification of the related substances in cisatracurium besylate for injection by LC-MS[J]. Journal of China Pharmaceutical University, 2013, 44(1): 65-72. DOI: 10.11665/j.issn.1000-5048.20130111
    [8]KONG Xing-xin, SHEN Wen-bin, WANG Li-yun, SHI Jin-fang, DI Bin, ZHANG Tao. Identification of the related substances in cefmetazole sodium by LC-MS/MS[J]. Journal of China Pharmaceutical University, 2012, 43(2): 170-176.
    [9]QIN Fang, DING Ya, HANG Tai-jun, SONG Min. Identification of the related substances in faropenem sodium by LC-MS/MS[J]. Journal of China Pharmaceutical University, 2011, 42(4): 342-347.
    [10]TIAN Yuan, FENG Shu-dan, HUANG Mei-hua, ZHANG Zun-jian. LC-MS/MS determination of glucocorticoids illegally added into cosmetics[J]. Journal of China Pharmaceutical University, 2011, 42(1): 53-57.

  • Cited by

    Periodical cited type(2)

    1. 王圆超，赵辉，王月，谷岩翡，高月麒，李晓露. 他克莫司的分离提纯研究. 中国抗生素杂志. 2024(02): 175-180 .
    2. 楚士颖，周玉松，张怡铭，唐雨晴，朱思宇，程文播. 液相色谱-串联质谱法同时测定血清中四种免疫抑制剂的药物浓度. 中国当代医药. 2024(09): 7-10+15 .

    Other cited types(0)

Catalog

    Get Citation
    PDF
    XML
    Article views (598) PDF downloads (950) Cited by(2)
    Turn off MathJax
    Article Contents
    Abstract
    References
    Related Articles

    Copyright © Journal of China Pharmaceutical University苏ICP备12050101号-2

    Address：24 Tongjia Lane, Nanjing City, Jiangsu Province （210009）Tel: 025-83271566E-mail: xuebao@cpu.edu.cn

    Supported by: Beijing Renhe Information Technology Co., Ltd.  Baidu Analytics

    Total visits：309727

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return