THE CELL-BINDING DOMAIN OF INTIMIN FROM ENTEROPATHOGENIC ESCHERICHIA-COLI BINDS TO BETA(1) INTEGRINS

Bacteria interact with mammalian cells surface mole cules, such as int egrins, to colonize tissues and evade immunological detection. Herein, the ability of intimin, an outer membrane protein from enteropathogen ic Escherichia coli, to bind beta(1) integrins was investigated. Solid -phase binding assays revealed binding of the carboxyl-terminal 280 am ino acids of intimin (Int280) to alpha(4) beta(1) and alpha(5) beta(1) integrins. The binding required divalent ions (in particular, it was enhanced by Mn2+) and was inhibited by an RGD-containing peptide. Nond erivatized Int280, but not Int280CS (like Int280 but with Cys-937 repl aced by Ser) blocked the binding of biotinylated Int280 to integrins. Int280 did not efficiently inhibit beta(1), integrin binding of invasi n from Yersinia pseudotuberculosis. Both intimin and invasin, immobili zed on plastic surfaces, mediated adherence of resting or phorbol 12-m yristate 13-acetate-activated human CD4(+) T cells, whereas fibronecti n mediated the adherence of only activated T cells. T cell binding to intimin and invasin was integrin mediated because it was specifically blocked by an RGD containing peptide and by antibodies directed agains t the integrin subunits beta(1), alpha(4) and alpha(5). These results demonstrate a specific integrin binding activity for intimin that is r elated to, but distinct from, that of invasin.