Anti-integrin monoclonal antibodies.

Adhesion that is mediated by integrins is controlled dynamically to allow cell positioning and migration and to prevent abnormal trafficking and anchorage. Integrin signalling in response to ligand binding is achieved by a combination of receptor clustering and conformational changes. Both of these processes can be elicited from the inside of the cell (resulting in the acquisition of a highaffinity receptor conformation and priming of the receptor for ligand binding) and from the outside (to mediate ligand-induced activation and signalling). The study of changes in integrin shape has been greatly aided by the availability of monoclonal antibodies (mAbs) that detect conformation-dependent epitopes. These mAbs have not only helped to pinpoint the intramolecular changes that determine the integrin activation state, but have also proven useful for regulating function. In recent years, major advances have been made in our understanding of the mechanisms that regulate integrin affinity (Arnaout et al., 2005; Luo et al., 2007) and, accordingly, we now also have an improved knowledge of the mechanisms of action of function-regulating mAbs. As these mAbs work in different ways, there is a danger that researchers might select the wrong reagent for their studies and/or misinterpret the data that they obtain. In this Cell Science at a Glance article, we have therefore attempted to explain briefly the mechanisms of antibody regulation of integrins. The accompanying poster lists three classes of key reagents: those that inhibit ligand engagement; those that stimulate ligand engagement or report a high-affinity integrin state (‘activation specific’); and those that serve as equally important negative controls. Partly owing to space constraints and partly owing to a lack of available information, we have restricted our selection of mAbs to those that recognise human integrins. Furthermore, 4009 Cell Science at a Glance