Definition, genetics, and possible significance of a newly defined endothelial antigen in the rat.

The purpose of the present experiments was to define a non-major-histocompatibility-complex (MHC) endothelial antigen system in the rat and to study the genetics of these antigens as well as their significance in renal transplantation. Several MHC-identical rat strain combinations underwent reciprocal immunization using spleen and lymph node cells and complete Freund's adjuvant. In one combination (MAXX anti-BN) alloantibodies were found against antigens on peritubular and venous endothelium of the kidney from the immunizing strain as well as from two other strains. Preliminary results suggested that the endothelial antigen is present on monocytes but not on nonstimulated T and B lymphocytes. With kidneys from 7 MHC-congenic lines it was shown that the endothelial antigens are encoded outside the MHC-region. The antigen seems to be expressed as a dominant trait. In an F2 population of 32 animals, segregation of the endothelial antigen or antigens appeared to be independent of the MHC, AgF, and tubular basement membrane antigens--as well as the locus for albinism. Transplantation of MHC-identical but endothelial-antigen-incompatible kidneys into nonimmunized recipients did not provoke acute rejection. Pretransplant immunity against donor endothelial antigens was, however, associated with accelerated acute rejection. The rejection was donor-specific because third-party MHC-incompatible but endothelial-antigen-compatible kidneys were rejected like first-set grafts. This model shows that graft rejection in presensitized recipients of an MHC-identical kidney can be mediated through immunity against non-MHC antigens.