A breeding program has been carried out starting with two miniature pigs from different sources and selecting offspring according to tissue typing procedures aimed at defining the major histocompatibility comples of this species. By this procedure three herds of miniatrue swine, and 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 tissue typing and transplantation; 2) Purification and characterization of the major histocompatibility antigens of this species, and isolation and characterization of peptides from these anitgens for sequence analyses and for assessment of immunologic reactivity; 3) Assessment of the immunologic parameters involved in tolerance to allografts in this species; 4) Detection and characterization of intro-MHC recombinants. Two intra-Mhc recombinants have been obtained and bred to homoqygosity. 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. An additional MHC recombinant has been obtained recently which appears to provide a new combination of Class I and Class II genes; 5) Bone marrow transplants in miniature swine. The effect of mixing autologous plus allogenic marrow in the reconstituting inoculum are being examined. This modality is being assessed as a specific prepartive regimen for allogenic organ transplanation; and 6) Production and characterization of monoclonal antibodies reactive with substs 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.
