The Immunosuppressive Effect of Passively Administered Antibody IgG Fragments

Summary The immunosuppressive effect of hyperimmune anti-KLH IgG fragments on the primary response of rabbits to KLH has been studied using three different antibody fragment preparations: bivalent F(ab′)2, univalent Fab′, and a mixture of univalent and bivalent F(ab′)2 (F(ab′)2 reduced and oxydized). The precipitating activities and antigen-binding capacities of these three antibody fragment preparations were compared on a molar basis with those of intact antibody IgG. The relative avidity of the fragments was very similar to that of intact antibody IgG as estimated by the effect of antigen dilution upon the binding capacity and by the dissociation rate of radiolabeled KLH-anti-KLH complexes in presence of an excess of unlabeled antigen. Both bivalent and univalent fragments inhibited the primary response of rabbits to KLH. When immunosuppressive antibody preparations were injected intravenously, repeated injections of antibody fragments were necessary to reach a degree of immunosuppression as great as that produced by a single injection of antibody IgG, because the fragments were rapidly eliminated. With a single intravenous injection of anti-KLH F(ab′)2, no greater than 85% suppression of the immune response was obtained despite a several-fold increase in the antibody dose injected, suggesting that KLH immunogenic molecules were not all accessible to passive antibody 1 day after antigen injection. Despite an antigen-binding capacity, a relative avidity and a rate of elimination similar to those of bivalent F(ab′)2, univalent Fab′ injected intravenously had a lower immunosuppressive effect. On the other hand, Fab′ produced a much greater inhibition than did IgG or F(ab′)2 when these preparations were mixed in vitro with KLH before incorporation in adjuvant.