Ni H, Wilkins J A
Department of Internal Medicine, University of Manitoba, Canada.
Cell Adhes Commun. 1998 Jun;5(4):257-71. doi: 10.3109/15419069809040296.
Members of the beta 1 integrin family mediate cellular adherence to a wide range of extracellular and cell surface associated ligands. Conformational changes have been shown to be associated with integrin activation and ligand binding. Some studies suggest that there may be a restricted region of the beta 1 integrin that serves as the target for regulatory antibodies which can inhibit or stimulate integrin function. Here we identify an inhibitory epitope that is located at a distinct sight from that suggested for other inhibitory antibodies. Three different adhesion blocking antibodies, JB1A, C30B, and D11B bind to a peptide corresponding to residues 82-87 of the mature beta 1 chain. Mn++ inhibited the binding of JB1A to purified beta 1 integrin. In contrast the binding of several other antibodies to beta 1 were not influenced by these conditions. JB1A binding to purified peptide was also inhibited by Mn++ suggesting that it related to interference with the antibody function rather than a cation dependent change in the epitope. Our data 1) directly demonstrates the peptide sequence recognised by three adhesion blocking antibodies to the human beta 1 integrin chain 2) identifies a novel epitope located at residues 82-87, distinct from that of previously described regulatory epitopes 3) characterises a Mn++ sensitive antibody integrin interaction. Collectively, these results indicate the existence of multiple regulatory sites on the beta 1 integrin molecule.
