The dominant role of la antibodies in the passive enhancement of H‐2 incompatible skin grafts

Abstract

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.

The role of B cells and alloantibody in the host response to human organ allografts

“…Rats treated with antibody did develop an antibody response, suggesting that the mechanism of enhancement was not inhibition of the antibody response. The antibody responsible for enhancement in rat systems was often anti‐class II (54). This finding led to the concept that anti‐class II is enhancing, because it damages the class II‐positive interstitial dendritic cells (IDCs), which are important immunogens but are not expressed on rat microvasculature, the target of AMR (55).…”

Ia‐Like Antigens of Rhesus Monkeys: Current State of Serology and Genetics

“…As for the biological significance of the la-like antigens of primates, 16 BALNER, VAN VRBESWIJK & ROGER work in progress at this laboratory is aimed at improving the serological definition of the antigens in order to (eventually) determine their role in immunobiology. Of particular interest should be the results of current experiments to establish whether matching for Ia-Iike antigens is relevant to histocompatibility, and whether the antibodies identifying those antigens have the 'enhancing' capacity described for la-antibodies in certain allograft models in rodents (Davies et al 1974, Staines et al 1975.…”

Antigen‐Reactive Cell Opsonization (ARCO) and its Role in Antibody‐Mediated Immune Suppression

“…The original demonstration that absorption of enhancing sera with donor erythrocytes does not abolish its activity (Davies & Alkins 1973) has been well confirmed in different systems (Staines et al 1975, Soulillou et al 1976. While these studies indicate that anti-donor la antibodies can very effectively enhance, they do not prove that anti-SD antibodies cannot.…”