Identification of a novel anti‐integrin monoclonal antibody that recognises a ligand‐induced binding site epitope on the β1 subunit

FEBS Letters

Mould, A.Paul¹  Akiyama, Steven K.²  Garratt, Alistair N.¹  Askari, Janet A.¹  Humphries, Martin J.¹ 

[1] School of Biological Sciences, University of Manchester, Manchester, M13 9PT, UK;Laboratory of Developmental Biology, NIDR, NIH, Bethesda, MD 20892, USA

关键词: Integrin;    Activation;    Ligand binding;    Monoclonal antibody;    Conformational change;    LIBS;    ligand-induced binding site(s);    CCBD;    central cell binding domain of fibronectin;    mAb;    monoclonal antibody;    kDa;    kilodalton;    H/120;    recombinant fragment of fibronectin that lacks the CCBD;    HBSS;    Hank's balanced salt solution;    PBS;    phosphate-buffered saline;    BSA;    bovine serum albumin;    ELISA;    enzyme-linked immunosorbent assay;    ABTS;    2;    2′-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid);    S.D.;    standard deviation;   

DOI  :  10.1016/0014-5793(95)00301-O

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Integrins are the major family of receptors involved in the adhesive interactions of cells with extracellular matrix macromolecules. Although it is known that integrins can exist in active or inactive states, the molecular mechanisms by which integrin activity is modulated are poorly understood. A novel anti-integrin monoclonal antibody, 12G10, that enhances α5β1-fibronectin interactions has been identified. 12G10 binds to the β1 subunit and appears to recognise a region of the subunit that contains the epitopes of several previously described activating or inhibitory monoclonal antibodies. However, unlike other activating anti-β1 antibodies, the binding of 12G10 to α5β1 is increased in the presence of ligands (fibronectin fragment or RGD peptide). This is the first report for the β1 integrin family of an antibody that recognises a ligand-induced binding site, and further emphasises the functional importance of a specific region of the β1 subunit in regulating integrin-ligand interactions.

【 授权许可】

Unknown