DICP OpenIR
Subject Area物理化学
Identification, Characterization, and Epitope Mapping of Human Monoclonal Antibody J19 That Specifically Recognizes Activated Integrin alpha(4)beta(7)
Qi, JunPeng1; Zhang, Kun1; Zhang, Qiao1; Sun, Yi1; Fu, Ting2; Li, GuoHui2; Chen, JianFeng1; ChenJianFeng
Source PublicationJOURNAL OF BIOLOGICAL CHEMISTRY
2012-05-04
ISSN0021-9258
DOI10.1074/jbc.M112.341263
Volume287Issue:19Pages:15749-15759
Indexed BySCI
SubtypeArticle
Department11
Funding Project1106
Contribution Rank2,5
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
WOS SubjectBiochemistry & Molecular Biology
WOS Research AreaBiochemistry & Molecular Biology
WOS KeywordPOLYMERASE CHAIN-REACTION ; ALPHA-I DOMAIN ; LYMPHOCYTE MIGRATION ; AVIDITY REGULATION ; OVERLAP EXTENSION ; STRUCTURAL BASIS ; PHORBOL ESTER ; CELL-ADHESION ; FIRM ADHESION ; OUTSIDE-IN
AbstractIntegrin alpha(4)beta(7) is a lymphocyte homing receptor that mediates both rolling and firm adhesion of lymphocytes on vascular endothelium, two of the critical steps in lymphocyte migration and tissue-specific homing. The rolling and firm adhesions of lymphocytes rely on the dynamic shift between the inactive and active states of integrin alpha(4)beta(7), which is associated with the conformational rearrangement of integrin molecules. Activation-specific antibodies, which specifically recognize the activated integrins, have been used as powerful tools in integrin studies, whereas there is no well characterized activation-specific antibody to integrin alpha(4)beta(7). Here, we report the identification, characterization, and epitope mapping of an activation-specific human mAb J19 against integrin alpha(4)beta(7). J19 was discovered by screening a human single-chain variable fragment phage library using an activated alpha(4)beta(7) mutant as target. J19 IgG specifically bound to the high affinity alpha(4)beta(7) induced by Mn2+, DTT, ADP, or CXCL12, but not to the low affinity integrin. Moreover, J19 IgG did not interfere with alpha(4)beta(7)-MAdCAM-1 interaction. The epitope of J19 IgG was mapped to Ser-331, Ala-332, and Ala-333 of beta(7) I domain and a seven-residue segment from 184 to 190 of alpha(4)beta-propeller domain, which are buried in low affinity integrin with bent conformation and only exposed in the high affinity extended conformation. Taken together, J19 is a potentially powerful tool for both studies on alpha(4)beta(7) activation mechanism and development of novel therapeutics targeting the activated lymphocyte expressing high affinity alpha(4)beta(7).
Language英语
WOS IDWOS:000304006300053
Citation statistics
Cited Times:3[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://cas-ir.dicp.ac.cn/handle/321008/117857
Collection中国科学院大连化学物理研究所
Corresponding AuthorChenJianFeng
Affiliation1.Chinese Acad Sci, Inst Biochem & Cell Biol, State Key Lab Cell Biol, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China
2.Chinese Acad Sci, Lab Mol Modeling & Design, State Key Lab Mol React Dynam, Dalian Inst Chem Phys, Dalian 116023, Peoples R China
Recommended Citation
GB/T 7714
Qi, JunPeng,Zhang, Kun,Zhang, Qiao,et al. Identification, Characterization, and Epitope Mapping of Human Monoclonal Antibody J19 That Specifically Recognizes Activated Integrin alpha(4)beta(7)[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2012,287(19):15749-15759.
APA Qi, JunPeng.,Zhang, Kun.,Zhang, Qiao.,Sun, Yi.,Fu, Ting.,...&ChenJianFeng.(2012).Identification, Characterization, and Epitope Mapping of Human Monoclonal Antibody J19 That Specifically Recognizes Activated Integrin alpha(4)beta(7).JOURNAL OF BIOLOGICAL CHEMISTRY,287(19),15749-15759.
MLA Qi, JunPeng,et al."Identification, Characterization, and Epitope Mapping of Human Monoclonal Antibody J19 That Specifically Recognizes Activated Integrin alpha(4)beta(7)".JOURNAL OF BIOLOGICAL CHEMISTRY 287.19(2012):15749-15759.
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