Increased expression of major histocompatibility complex (MHC) class I transplantation antigens in bovine trophoblast cells before fusion with maternal cells
Bainbridge DR., Sargent IL., Ellis SA.
<jats:p>The mammalian fetus is potentially at risk from maternal immune attack because it can express paternally inherited polymorphic antigens, including those encoded by the major histocompatibility complex (MHC). The aim of this study was to investigate in more detail MHC class I upregulation by binucleate trophoblast cells in the bovine placenta. A method was developed to isolate binucleate cells by enzymatic disaggregation and density gradient centrifugation of bovine placental cotyledons. In cytospin preparations, 25-30% of purified binucleate cells stained positively with antibodies that recognize bovine MHC class I. The same antibodies were used to immunoprecipitate radiolabelled class I molecules from lysates of binucleate cells and fetal peripheral blood mononuclear cells. The protein species isolated from the two types of cell were similar in size and degree of glycosylation. PCR amplification of cDNA generated from binucleate cells and subsequent sequence analysis demonstrated transcription of MHC class I mRNA species similar to those found in fetal peripheral blood mononuclear cells, and there was no evidence of genetic imprinting of paternally inherited alleles. These results indicate that binucleate cells upregulate expression of MHC class I as they differentiate from MHC-negative uninucleate trophoblast cells. This finding has important implications for the immunological status of the fetus, as binucleate trophoblast cells are destined to cross to the maternal side of the placenta where they fuse with maternal cells. The immunological function of the resulting antigenically mixed fetomaternal hybrid minisyncytia is unknown.</jats:p>