CONTROL OF BETA(1) INTEGRIN FUNCTION - LOCALIZATION OF STIMULATORY EPITOPES

The beta(1) integrins can be expressed on the surface of cells in a la tent form, which is activated by a variety of stimuli, As an approach to examining the transition to an active receptor, a panel of stimulat ory antibodies to beta(1) were produced and characterized, These antib odies induced adherence of the T-leukemic cell line Jurkat to collagen and fibronectin, Competitive antibody binding assays indicated the ex istence of at least three distinct epitope clusters A (B3B11, JB1B, 21 C8), B (B44, 13B9), and C (N29) defined by the indicated antibodies, T wo antibodies to the A site, JB1B and B3B11, were shown to localize to positions 671-703 and 657-670, respectively, of the beta(1). This reg ion is located in an area encompassing a predicted disulfide bond betw een linearly distant cysteines in beta(1) (Cys(415)-Cys(671)). The hom ologous region of the beta(3) integrin (490-690 and 602-690) has been shown to be one of the sites recognized by stimulatory antibodies to l igand-induced binding sites. The present results indicate the existenc e of multiple stimulatory regions and suggest considerable homology be tween the locations of beta(1) and beta(3) regulatory sites.