The objectives of this project are to explore the nature of the antibody response to the placenta and the antigen(s) eliciting it by using immunological, genetic and biochemical techniques and inbred, congenic and recombinant rats. The hypothesis to be tested is that an antigen unique to the placenta and most likely encoded by a gene(s) in the major histocompatibility complex elicits the antibody response and that this response affects reproductive capacity. There are three specific aims. First, the structure and location on the placenta of the antigen carrying the determinant eliciting the antibody response to the fetus will be determined by biochemical and immunohistochemical techniques using pregnancy sera and monoclonal antibodies obtained from hybridomas made by fusing splenic lymphocytes from pregnant animals with the P3-653 myeloma cells. Second, the antibody response to the antigens of the feto-placental unit will be investigated systematically. The strain combinations in which the response is elicited will be identified, and the litter sizes of the various matings will be correlated with the presence or absence of an antibody response. Third, the genetic control of the maternal antibody response to the fetal antigens will be examined. The number of genes involved will be evaluated by examining the antibody responses in the backcross progeny of a responder x nonresponder cross and using gene modeling techniques. The significance of these experiments lies in their providing basic knowledge about the immunological and genetic aspects of the maternal-fetal interaction and its consequences for reproduction. The rat is the unique experimental animal with which to investigate these problems because of its greatly limited polymorphism, the large amount of tissue available for biochemical studies and the availability of all of the necessary resources in our laboratory. These studies will provide insight into the evolutionary significance of heterozygosity (heterosis) and its influence on reproductive capacity and into the nature of the antigens on the interface between the placenta and the maternal circulation. This information will fill a critical gap in our understanding of the maternal immune response to the conceptus, and it will provide the background for similar studies in humans at a later date.
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