Lack of CIITA expression is central to the absence of antigen presentationfunctions of trophoblast cells and is caused by methylation of the IFN-gamma inducible promoter (PIV) of CIITA

Lack of MHC-mediated antigen presenting functions of fetal trophoblast cell s is an important mechanism to evade maternal immune recognition. In this s tudy we demonstrated that the deficiency in MHC expression and antigen pres entation in the trophoblast cell lines JEG-3 and JAR is caused by lack of c lass II transactivator (CIITA) expression due to hypermethylation of its in terferon-gamma (IFN-gamma)-responsive promoter (PIV). Circumvention of this lack of CIITA expression by introduction of exogenous CIITA induced cell s urface expression of HLA-DR, -DP, and -DQ, leading to an acquired capacity to present antigen to antigen-specific T cells. Transfection of CIITA in JE G-3 cells also upregulated functional HLA-B and HLA-C expression. Noteworth y, this lack of IFN-gamma -mediated induction of CIITA was also found to ex ist in normal trophoblast cells expanded from chorionic villus biopsies. To gether, these observations demonstrate that lack of CIITA expression is cen tral to the absence of antigen presentation functions of trophoblast cells. Human Immunology BI, 850-862 (2000). (C) American Society for Histocompati bility and Immunogenetics, 2000. Published by Elsevier Science Inc.