CD4-BINDING COMPOUNDS - AN ASSAY TO DETECT NEW CLASSES OF IMMUNOPHARMACOLOGICAL AGENTS

The interaction of antibodies with protein antigens is accepted as a p aradigm of protein - protein interactions. In searching for a new gene ration of immunomodulatory compounds based on the interaction of the T -cell surface glycoprotein CD4 with MHC class II antigens, a model ass ay has been developed in which MHC molecules have been substituted by a monoclonal antibody (anti-Leu3a) to the CD4 amino-terminal domain-sp ecific epitope, Leu3a. This assay can detect diverse classes of molecu les including proteins such as HIV envelope glycoprotein gp120 and low molecular weight compounds such as aurin tricarboxylic acid, dextran sulphate and Evans blue. The interaction of these molecules with CD4 i n the assay appears to be identical to their interaction with native C D4 on intact cells. Other protein - antibody pairs could be substitute d for CD4 - anti-Leu3a enabling this assay format to be used for the d etection of proteins or small organic compounds which interfere with a wide range of therapeutically-relevant macromolecular interactions.