Withdrawn

Abstract

The expression pattern of MHC class I genes in trophoblast cells at the feto–maternal interface is thought to be the basis of the maintenance of pregnancy by protecting the fetus from maternal immune rejection. Transcription of classical HLA class I genes is low or undetectable in most trophoblast cells as well as in JEG-3 and BeWo trophoblast-derived choriocarcinoma cells. The aim of this study was to characterize the regulatory mechanisms that repress HLA-A transcription in these cell types. We show that the −335 to ATG region of the HLA-A11 gene promoter is inactive in JEG-3 and BeWo cells while able to control efficient reporter gene transcription in other cell types, indicating that this region is the target for downregulation of HLA-A expression in choriocarcinoma cell lines. The regulatory sequence involved in HLA-A gene repression was further mapped to a proximal regulatory element within the −107 to +2 ATG region of the promoter. We show that the HLA-A promoter activity cannot be induced by interferon-γ (IFN-γ) and that exogenous MHC class II transactivator CIITA is able to induce HLA class I promoter activity in these cells. Stringent transcriptional regulatory mechanisms, implicating the lack of basal and IFN-γ-inducible class I promoter activity, are thus involved in the downregulation of HLA-A expression in JEG-3 and BeWo trophoblast-derived choriocarcinoma cells.