Posttranscriptional regulation of human leukocyte antigen G during human extravillous cytotrophoblast differentiation

Human maternal tolerance to a semiallogenic fetus may be maintained, in par t, by the unusual expression pattern of antigen-presenting molecules in pla cental trophoblast cells. Extravillous cytotrophoblast (EVC) cells, which i nvade the maternal decidua, express high levels of human leukocyte antigen C (HLA-G), a nonclassical, major histocompatibility complex (MHC) class I m olecule. HLA-C transcripts have been detected in tumors and other tissues, yet protein accumulation is rare. We show that, within EVC cells themselves , the mRNA is more broadly expressed than the protein. Specifically, accumu lation of HLA-G protein was markedly delayed during EVC cell differentiatio n. To elucidate this mechanism, we performed a comprehensive analysis compa ring the expression of HLA-G and proteins essential for MHC class I express ion at the cell surface. The transporter for antigen processing proteins TA P1 and TAP2, as well as tapasin and beta(2)-microglobulin, appeared to be c oordinately expressed throughout EVC cell columns. Strikingly, they all acc umulated well in advance of the HLA-G protein but concurrently with its mRN A. A similar delay in the accumulation of the HLA-G protein was observed in vitro, using cultures of chorionic villi. We conclude that posttranscripti onal regulation of HLA-G is fundamental to EVC cell development and is achi eved independently of the peptide loading system. This represents a novel m echanism of MHC class I regulation.