Identification, Characterization, and Epitope Mapping of Human Monoclonal Antibody J19 That Specifically Recognizes Activated Integrin alpha(4)beta(7)

	Identification, Characterization, and Epitope Mapping of Human Monoclonal Antibody J19 That Specifically Recognizes Activated Integrin alpha(4)beta(7)
	Qi, JunPeng 1; Zhang, Kun 1; Zhang, Qiao 1; Sun, Yi 1; Fu, Ting 2; Li, GuoHui 2; Chen, JianFeng 1
刊名	journal of biological chemistry
	2012-05-04
卷号	287 期号:19 页码:15749-15759
ISSN号	0021-9258
通讯作者	chenjianfeng
产权排序	2,5
英文摘要	integrin 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).
学科主题	物理化学
WOS标题词	science & technology ; life sciences & biomedicine
类目[WOS]	biochemistry & molecular biology
研究领域[WOS]	biochemistry & molecular biology
关键词[WOS]	polymerase chain-reaction ; alpha-i domain ; lymphocyte migration ; avidity regulation ; overlap extension ; structural basis ; phorbol ester ; cell-adhesion ; firm adhesion ; outside-in
收录类别	SCI
语种	英语
WOS记录号	WOS:000304006300053
公开日期	2013-10-11
内容类型	期刊论文
源URL	[http://159.226.238.44/handle/321008/117857]
专题	大连化学物理研究所_中国科学院大连化学物理研究所
作者单位	1.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
推荐引用方式 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.,...&Chen, JianFeng.(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.