The dominant role of Ia antibodies in the passive enhancement of H-2 incompatible skin grafts.

The ability of H-2 antisera and their constituent K and Ia antibodies to enhance the survival of skin allografts was investigated. Ia sera were prepared from H-2 alloantisera by exhaustive absorption with donor-strain RBC and the absorbed K antibodies were also recovered by acid elution of the RBC. The removal of conventional K/D antibody in no way diminished the activity of enhancing sera over wide dose ranges in two different incompatibility systems. The recovered K/D antibodies in the doses used had at best a trivial enhancing effect. The dominant role of Ia antibodies in enhancement was confirmed by showing significant prolongation of graft survival in third-party systems where the sera covered only some of the Ia antigens in incompatibilities involving K,D and Ia differences and in homologous systems using Ia sera fractionated into their constituent mono-specificities. It is concluded that enhancement is a function of antibodies directed against Ia antigens (I region products) and that antibody against conventional histocompatibility antigens such as H-2.K, D, and by homology HL-A and Ag-B has only a minor role in passive enhancement.