Prolonged survival of corneal allografts incubated in alloantibody fragments

Background. In this study, we determined the binding characteristics of F(a b')(2) alloantibody fragments to corneal antigens and assessed the capacity of these antibody fragments to protect corneal allografts from immune atta ck. Methods. Goat anti-rabbit alloantibodies were pepsin-digested and labeled w ith I-125, and the time course of association and dissociation of the F(ab' )(2) fragments was determined. Corneal allografts were incubated in unlabel ed F(ab')(2) fragments and transplanted into allogeneic recipients, and the graft survival times were recorded. Results. Binding of radiolabeled F(ab')(2) fragments to rabbit cornea cells reached a maximum at 12 hr. At 32 degrees C (rabbit corneal temperature), the radiolabel eluted rapidly from the cornea, reaching baseline at 72 hr. At 4 degrees C (corneal graft storage temperature), significant amounts rem ained associated with the cornea at 96 hr. Mean survival time for grafts in cubated in F(ab')(2) anti-rabbit fragments was significantly greater than t hat of grafts incubated in nonimmune F(ab')(2) fragments. Three of the corn eal allografts incubated in goat F(ab')(2) anti-rabbit fragments survived f or 100 days, whereas the longest surviving control allograft incubated in g oat F(ab')(2) nonimmune fragments was rejected on day 24. Preincubation of corneas in unlabeled, immune F(ab')(2) fragments followed by incubation in radiolabeled, immune F(ab')(2) fragments suggested that antigen masking was not a factor in the prolongation of graft survival. Conclusion. Based on the binding and release kinetics and the graft surviva l times, it appears that the protective effect of immune F(ab')(2) fragment s extends well beyond the binding interval of the antibody fragments to cor neal cell membranes.