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学科主题: 临床医学
题名:
The Protective Antibodies Induced by a Novel Epitope of Human TNF-alpha Could Suppress the Development of Collagen-Induced Arthritis
作者: Dong, Jie1; Gao, Yaping1; Liu, Yu1; Shi, Jinxia2; Feng, Jiannan1; Li, Zhanguo2; Pan, Heping1; Xue, Yanning1; Liu, Chuan1; Shen, Beifen1; Shao, Ningsheng1; Yang, Guang1
刊名: PLOS ONE
发表日期: 2010-01-27
DOI: 10.1371/journal.pone.0008920
卷: 5, 期:1
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Multidisciplinary Sciences
研究领域[WOS]: Science & Technology - Other Topics
关键词[WOS]: TUMOR-NECROSIS-FACTOR ; RHEUMATOID-ARTHRITIS ; HUMAN-DISEASES ; ANTAGONIST ; ADALIMUMAB ; INHIBITOR ; BLOCKADE ; EFFICACY ; THERAPY ; SAFETY
英文摘要:

Tumor necrosis factor alpha (TNF-alpha) is a major inflammatory mediator that exhibits actions leading to tissue destruction and hampering recovery from damage. At present, two antibodies against human TNF-alpha (hTNF-alpha) are available, which are widely used for the clinic treatment of certain inflammatory diseases. This work was undertaken to identify a novel functional epitope of hTNF-alpha. We performed screening peptide library against anti-hTNF-alpha antibodies, ELISA and competitive ELISA to obtain the epitope of hTNF-alpha. The key residues of the epitope were identified by means of combinatorial alanine scanning and site-specific mutagenesis. The N terminus (80-91 aa) of hTNF-alpha proved to be a novel epitope (YG1). The two amino acids of YG1, proline and valine, were identified as the key residues, which were important for hTNF-alpha biological function. Furthermore, the function of the epitope was addressed on an animal model of collagen-induced arthritis (CIA). CIA could be suppressed in an animal model by prevaccination with the derivative peptides of YG1. The antibodies of YG1 could also inhibit the cytotoxicity of hTNF-alpha. These results demonstrate that YG1 is a novel epitope associated with the biological function of hTNF-alpha and the antibodies against YG1 can inhibit the development of CIA in animal model, so it would be a potential target of new therapeutic antibodies.

语种: 英语
所属项目编号: 2010CB529100 ; 30700007 ; 30870093 ; 2006AA02Z132 ; 2006AA02Z323 ; 2006AA02A253
项目资助者: Chinese National Key Program on Basic Research ; National Natural Science Foundation of China ; National High-Tech Research and Development Program
WOS记录号: WOS:000274114800022
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/52424
Appears in Collections:北京大学第二临床医学院_期刊论文

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作者单位: 1.Beijing Inst Basic Med Sci, Beijing, Peoples R China
2.Peking Univ, Peoples Hosp, Dept Rheumatol & Immunol, Beijing 100871, Peoples R China

Recommended Citation:
Dong, Jie,Gao, Yaping,Liu, Yu,et al. The Protective Antibodies Induced by a Novel Epitope of Human TNF-alpha Could Suppress the Development of Collagen-Induced Arthritis[J]. PLOS ONE,2010,5(1).
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