Three herds of miniature swine, each homozygous for a different set of histocompatibility antigens at the MHC have been developed. Current projects include: 1) Assessment of survival of organs and tissue transplants among and between members of these herds as a model for human transplantation; 2) Assessment of the immunologic parameters involved in tolerance to allografts in this species; 3) Detection and characterization of intra-MHC recombinants: Five intra-MHC recombinants have been obtained and have been or are being bred to homozygosity. Kidney transplants utilizing these new recombinants have shown that selective matching for Class II antigens frequently permits long-term kidney graft survival across a Class I difference; 4) Bone marrow transplants in miniature swine: the effect of mixing autologous plus allogeneic marrow in the reconstituting inoculum are being examined. This modality is being assessed as a specific preparative regimen for allogeneic organ transplantation; 5) Production and characterization of monoclonal antibodies reactive with subsets of pig lymphocytes: antibodies corresponding to many of the OKT series in man have been identified (including T4, T8, and T11). The effects of these antibodies on in vitro and in vivo transplantation immunity are being assessed, and they are also being used to assess mechanism of tolerance; and 6) Analysis of class II MHC genes: Southern blot analyses using cDNA probes from human class II genes have been performed and indicate that genes corresponding to each of the major human class II loci are present in the pig genome. In addition, a genomic library and two cDNA libraries have been constructed and screened with these probes. Class II genes from the pig herds have been isolated and characterized by hybridization and by sequence analysis. These genes have also been used in vitro and in vivo for transfection studies, and have been incorporated into retroviral constructs for transduction of bone marrow cells.
