title: Lack of CIITA expression is central to the absence of antigen presentation functions of trophoblast cells and is caused by methylation of the IFN-gamma inducible promoter (PIV) of CIITA.
abstract: Lack of MHC-mediated antigen presenting functions of fetal trophoblast cells is an important mechanism to evade maternal immune recognition. In this study we demonstrated that the deficiency in MHC expression and antigen presentation in the trophoblast cell lines JEG-3 and JAR is caused by lack of class II transactivator (CIITA) expression due to hypermethylation of its interferon-gamma (IFN-gamma)-responsive promoter (PIV). Circumvention of this lack of CIITA expression by introduction of exogenous CIITA induced cell surface expression of HLA-DR, -DP, and -DQ, leading to an acquired capacity to present antigen to antigen-specific T cells. Transfection of CIITA in JEG-3 cells also upregulated functional HLA-B and HLA-C expression. Noteworthy, this lack of IFN-gamma-mediated induction of CIITA was also found to exist in normal trophoblast cells expanded from chorionic villus biopsies. Together, these observations demonstrate that lack of CIITA expression is central to the absence of antigen presentation functions of trophoblast cells.
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands. pvdelsen@euronet.nl
authors.forename: P J
authors.initials: PJ
authors.lastname: van den Elsen
authors.forename: N
authors.initials: N
authors.lastname: van der Stoep
authors.forename: H E
authors.initials: HE
authors.lastname: Viëtor
authors.forename: L
authors.initials: L
authors.lastname: Wilson
authors.forename: M
authors.initials: M
authors.lastname: van Zutphen
authors.forename: S J
authors.initials: SJ
authors.lastname: Gobin
mesh_terms: D017951:Antigen Presentation / Q000276:immunology*; D002460:Cell Line; D002461:Cell Line, Transformed; D002822:Choriocarcinoma; D002824:Chorionic Villi; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006680:HLA Antigens / Q000096:biosynthesis; D006367:HeLa Cells; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000494:pharmacology; D020014:K562 Cells; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D000071701:Regulatory Factor X Transcription Factors; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics; D014162:Transfection; D014327:Trophoblasts / Q000166:cytology / Q000276:immunology*
chemical_list: D004268:DNA-Binding Proteins; D006680:HLA Antigens; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; C093524:RFX5 protein, human; C413004:RFXAP protein, human; D000071701:Regulatory Factor X Transcription Factors; D015534:Trans-Activators; D014157:Transcription Factors; D007371:Interferon-gamma