In vivo and in vitro interactions between idiotypic and antiidiotypic monoclonal antibodies against placental alkaline phosphatase

Abstract

A monoclonal antiidiotypic antibody alpha H7, was generated against a monoclonal antibody H7 with specificity towards placental alkaline phosphatase. The in vitro and in vivo effects of alpha H7 were investigated. The antiidiotypic antibody was found to generate stable complexes with the radiolabeled idiotypic antibody, visualized both in vivo and in vitro, as revealed by PAGE and autoradiography. Using biosensor technology (BIAcore, Pharmacia) the interactions were followed in real time and the association rate, dissociation rate, and affinity constants between the reactants were determined (KA H7/PLAP 6.7 x 10(9) M-1, KA H7/alpha H7 3.2 x 10(9) M-1). By in vivo injection of the antiidiotype, a rapid dose dependent clearance of circulating radiolabeled idiotypes was demonstrated and a decrease in total body radioactivity was recorded with a concomitant dramatic increase in non-protein-bound 125I excreted in the urine. It is concluded that idiotypic-antiidiotypic interactions offer advantages in the regulation of antibody levels in vivo.