Repression of Major Histocompatibility Complex Genes by a Human Trophoblast Ribonucleic Acid

The suppression of polymorphic major histocompatibility complex antigen expression in human trophoblasts is critical for the avoidance of a cell-mediated immune response by maternal lymphocytes against cells expressing paternal antigens. In this study, a repressor of major histocompatibility complex gene expression was cloned by negative immunoselection using a trophoblast cDNA expression library in interferon-gamma-responsive human cells. The sequence of this regulatory gene was analyzed, and the functions of the transfected cDNA or microinjected gene product were examined in interferon-gamma-responsive cells by immunocytochemical methods. The repressor, called TSU-- trophoblast STAT (signal transducers and activators of transcription) utron (untranslated region of an mRNA)--reduced STAT1 nuclear translocation and suppressed major histocompatibility complex class II antigen expression at high doses of interferon-gamma and class I expression at low doses of interferon-gamma. TSU encoded a small, untranslated poly-A+-RNA that appeared to bind STAT1 through pairs of motifs analogous to STAT-binding promoter sequences. These promoter-like motifs, but no open reading frame, were conserved in a TSU-related gene in goats. Northern blot analysis demonstrated that TSU was expressed as a 0. 5-kilobase (kb) RNA in placenta and as an ubiquitous 4.4-kb RNA. TSU expression may protect trophoblasts from immune attack and promote the survival of the placenta and fetus.