MHC class II gene silencing in trophoblast cells is caused by inhibition of CIITA

MHC class II molecules function in the presentation of foreign antigens to T lymphocytes and therefore play a critical role in the initiation of the immune response. Although constitutive MHC class II gene expression is restricted to antigen presenting cells, class II gene expression can be induced in a variety of cell types by IFN-γ. This induction is not seen at the fetal-maternal boundary during pregnancy, and the lack of class II induction has been suggested to play a role in preventing rejection of the fetal allograft. We have investigated the mechanism of class II gene repression in trophoblast cells, which comprise the embryonic portion of the placenta. These cells do not upregulate class II gene expression in response to IFN-γ treatment. RT-PCR analysis revealed that the lack of class II transcription is not due to the absence of expression of two class II transcription factors, nor is it due to a lesion in the IFN-γ signaling pathway, but results from the inhibition of expression of the class II transactivator (CIITA). Transfection of a CIITA expression vector into trophoblast cells restored class II gene expression, demonstrating that repression of CIITA expression is the cause of class II gene silencing at the fetal-maternal boundary.