IDENTIFICATION OF A NOVEL ANTI-INTEGRIN MONOCLONAL-ANTIBODY THAT RECOGNIZES A LIGAND-INDUCED BINDING-SITE EPITOPE ON THE BETA-1 SUBUNIT

Integrins are the major family of receptors involved in the adhesive i nteractions of cells with extracellular matrix macromolecules. Althoug h it is known that integrins can exist in active or inactive states, t he molecular mechanisms by which integrin activity is modulated are po orly understood, A novel anti-integrin monoclonal antibody, 12G10, tha t enhances alpha 5 beta 1-fibronectin interactions has been identified . 12G10 binds to the beta 1 subunit and appears to recognise a region of the subunit that contains the epitopes of several previously descri bed activating or inhibitory monoclonal antibodies, However, unlike ot her activating anti-beta 1 antibodies, the binding of 12G10 to alpha 5 beta 1 is increased in the presence of ligands (fibronectin fragment or RGD peptide). This is the first report for the beta 1 integrin fami ly of an antibody that recognises a Ligand-induced binding site, and f urther emphasises the functional importance of a specific region of th e beta 1 subunit in regulating integrin-ligand interactions.