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Lymphocyte,CTL)表位富集区的方法,并以严重急性呼吸道综合征(SARS)相关冠状病毒(SARS-CoV)的M蛋白为例,成功地鉴定了一个HLA-A2限制性的表位富集区。首先通过生物信息学的方法预测并合成M蛋白跨膜区的HLA-A2潜在结合多肽,通过体外复性实验和T2细胞结合实验验证多肽与HLA-A2的结合力;然后在HLA-A2.1/Kb转基因小鼠中检测这些多肽的免疫原性;最后通过X射线衍射技术,成功解析了其中一条多肽与HLA-A*0201的复合物结构,其结构显示该多肽具有典型的HLA-A*0201表位的结构特点,但却呈现出与以往鉴定多肽不同的构象和锚定残基。本文对于理解机体对SARS-CoV等病原体产生的T细胞免疫反应,以及为更广泛的人群设计T细胞疫苗具有重要意义。, authors=刘军1, 齐建勋1, 高峰2, 严景华1, 高福1, authorsList=刘军;齐建勋;高峰;严景华;高福, authorCompany=1. 中国科学院微生物研究所病原微生物与免疫学重点实验室,北京 100101;2. 中国科学院生物物理研究所生物大分子国家重点实验室,北京 100101, correspAuthors=null, authorNote=null, correspAuthorsNote=高福(中国科协所属全国学会个人会员登记号:M200269402S),研究员,研究方向为病原微生物和结构免疫学,电子信箱:gaof@im.ac.cn, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=+v3QHf0UI6EnMCROLEeogw==, pdfFileSize=3547823, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, 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科技导报 |研究论文 2011 , 29 (27) : 19 -26
T细胞功能学与结构免疫学结合方法鉴定HLA-A2限制性的细胞毒性T淋巴细胞表位富集区
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刘军1, 齐建勋1, 高峰2, 严景华1, 高福1
作者信息
    1. 中国科学院微生物研究所病原微生物与免疫学重点实验室,北京 100101;2. 中国科学院生物物理研究所生物大分子国家重点实验室,北京 100101
通讯作者:
高福(中国科协所属全国学会个人会员登记号:M200269402S),研究员,研究方向为病原微生物和结构免疫学,电子信箱:gaof@im.ac.cn
Functional and Structural Definition of a Clustering Region of HLA-A2-restricted Cytotoxic T Lymphocyte Epitopes
  • LIU Jun1, QI Jianxun1, GAO Feng2, YAN Jinghua1, GAO George Fu1
  • Affiliations
      1. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China;2. National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
    出版时间: 2011-09-28 doi: 10.3981/j.issn.1000-7857.2011.27.001
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    T细胞表位在抗病毒的T细胞免疫中发挥核心作用,目前已在多种病原微生物的蛋白序列上发现存在T细胞表位的聚集现象。本文建立了一套功能学与结构学结合的策略鉴定病原体上细胞毒性T细胞(Cytotoxic T Lymphocyte,CTL)表位富集区的方法,并以严重急性呼吸道综合征(SARS)相关冠状病毒(SARS-CoV)的M蛋白为例,成功地鉴定了一个HLA-A2限制性的表位富集区。首先通过生物信息学的方法预测并合成M蛋白跨膜区的HLA-A2潜在结合多肽,通过体外复性实验和T2细胞结合实验验证多肽与HLA-A2的结合力;然后在HLA-A2.1/Kb转基因小鼠中检测这些多肽的免疫原性;最后通过X射线衍射技术,成功解析了其中一条多肽与HLA-A*0201的复合物结构,其结构显示该多肽具有典型的HLA-A*0201表位的结构特点,但却呈现出与以往鉴定多肽不同的构象和锚定残基。本文对于理解机体对SARS-CoV等病原体产生的T细胞免疫反应,以及为更广泛的人群设计T细胞疫苗具有重要意义。
    细胞免疫  /  表位富集区  /  主要组织相容性复合物  /  HLA-A2  /  晶体结构
    T cell epitopes play an important role in the anti-virus specific T cell immunity. Currently, the phenomenon of T cell epitope clustering is reported among different pathogenic microbes. Here, a strategy is established to identify Cytotoxic T Lymphocyte (CTL) epitope clusters region with the combined functional and structural methods. And by using this strategy, a HLA-A2-restricted epitope cluster in SARS-CoV M protein is successfully defined. Firstly, the computer-assisted algorithm was utilized to predict a series of potential HLA-A2 binding peptides around the sequences of two previous identified HLA-A2 epitopes Mn2 and Md3 in the transmembrane domain of SARS-CoV M protein. The HLA-A2 binding affinities of these peptides were accessed through in vitro refolding assay and T2 cell binding assay. Consequently, antigenicity of the peptides was confirmed by ELISPOT by using transgenic mice immunized with peptide Mn2 or DNA vaccine of M protein. Furthermore, the crystal structure of HLA-A*0201 complexed with peptide Md3-C9 was determined. And the structure shows that the peptide is presented in a traditional conformation of HLA-A2 restricted peptides, however is different from the previously-determined structure of Md3. The result is a great help to understand anti-virus T cell responses and might pave a new way for the T cell-related vaccines for a broader population.
    cell immunity  /  epitope clustering region  /  MHC  /  HLA-A2  /  crystal structure
    刘军;齐建勋;高峰;严景华;高福. T细胞功能学与结构免疫学结合方法鉴定HLA-A2限制性的细胞毒性T淋巴细胞表位富集区. 科技导报, 2011 , 29 (27) : 19 -26 . DOI: 10.3981/j.issn.1000-7857.2011.27.001
    LIU Jun;QI Jianxun;GAO Feng;YAN Jinghua;GAO George Fu. Functional and Structural Definition of a Clustering Region of HLA-A2-restricted Cytotoxic T Lymphocyte Epitopes[J]. Science & Technology Review, 2011 , 29 (27) : 19 -26 . DOI: 10.3981/j.issn.1000-7857.2011.27.001

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    doi: 10.3981/j.issn.1000-7857.2011.27.001
    • 接收时间:2011-08-23
    • 首发时间:2011-09-28
    • 出版时间:2011-09-28
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    • 收稿日期:2011-08-23
    • 修回日期:2011-09-04
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    高福(中国科协所属全国学会个人会员登记号:M200269402S),研究员,研究方向为病原微生物和结构免疫学,电子信箱:gaof@im.ac.cn
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    https://castjournals.cast.org.cn/joweb/kjdb/CN/10.3981/j.issn.1000-7857.2011.27.001
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    2种不同金属材料的力学参数

    Family
    属数
    Number of
    genus
    种数
    Number of
    species
    占总种数比例
    Percentage of
    total species (%)

    Genus
    种数
    Number of
    species
    占总种数比例
    Percentage of total
    species (%)
    鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
    小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
    多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
    红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
    小菇属 Mycena 11 5.26
    光柄菇属 Pluteus 5 2.39
    红菇属 Russula 17 8.13
    栓菌属 Trametes 5 2.39
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