Effect of the major histocompatibility complex on early mouse development
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Abstract
The class I molecules of the murine major histocompatibility complex (MHC), the H-2 complex, are of utmost importance in the recognition of self vs. nonself, and in the regulation of the immune response. In recent years, a great deal of interest has centered on the role of the MHC in nonimmune phenomena. Among these traits are those associated with reproduction and development. We have shown that a gene, Ped (preimplantation embryo development) is associated with the H-2 complex. Ped gene expression is apparent at the first cleavage division and affects the rate of subsequent cleavages. Therefore, the Ped gene product, whose nature is unknown, must be expressed at this time. It is possible that the Ped gene product is a class I molecule of the H-2 complex, and that the control of the rate of development is one of the many pleiotrophic effects of these cell surface molecules. The first goal of this dissertation was the development of a highly sensitive assay to detect class I antigens on the embryo cell surface. Using this assay, we have followed the expression of several MHC antigens during early embryo development. The de novo synthesis of MHC molecules by the embryos was proven by stripping the proteins off the cell surface with enzymes and measuring the reappearance of the antigens. One of the class I MHC antigens was purified and used in blocking studies to further confirm the presence of class I antigens on the embryonic cell surface;The second goal of this dissertation was to map the Ped gene within the mouse MHC. The data show that the Ped gene maps to the Qa-2 region of the H-2 complex. Classical segregation analysis was done to prove linkage of the Ped gene to the H-2 complex. Indeed, the Ped gene was shown to segregate with genes encoded in the H-2 complex. The function of Qa-2 antigens is unknown. Based on the work presented in this thesis, one of the Qa-2 antigens may be the Ped gene product.