EPITOPE MAPPING OF A FUNCTION-BLOCKING BETA-1 INTEGRIN ANTIBODY BY PHAGE DISPLAY

Integrins are a major class of cell surface receptors involved in cell -cell and cell-matrix adhesion and communication. Ha2/11 is a function -blocking anti-rat beta 1 integrin hamster IgM that should be a useful reagent for understanding pi integrin function. We demonstrate that H a2/11 cross reacts with human, Xenopus, and Drosophila beta 1 integrin s, and use phage display to map the epitope for Ha2/11 to residues wit hin the sequence LRSGEPQTF which lies 18 amino acids proximal to the p utative I domain in beta 1 integrins. Monoclonal antibody mapping expe riments, mutational analyses, and direct binding assays have implicate d integrin I domains in both cation and ligand binding. Our data there fore suggest that Ha2/11 blocks beta 1 integrin function by interferin g with I domain-mediated ligand binding.