Class II transactivator-independent endothelial cell MHC class II gene activation induced by lymphocyte adhesion.
NK cells induce MHC class II molecules on the surface of allogeneic endothelial cells in an adhesion-dependent, IFN-gamma-independent manner. Here, we demonstrate that NK cells induce HLA-DR on the surface of a mutant cell line that is defective in IFN-gamma-induced MHC class II expression. RNA analysis in these cells and in a cell line that is defective in class II transactivator (CIITA) demonstrates that NK cell-induced HLA-DR alpha mRNA expression is also CIITA-independent. The Janus kinase-1-deficient cell line U4A expresses HLA-DR alpha mRNA in response to NK cell activation, and HLA-DR alpha promoter constructs transfected into these cells are induced by NK cells but not IFN-gamma. These data indicate that the IFN-gamma-independent component of the target cell HLA-DR expression induced by lymphocyte adhesion uses a signaling pathway that is distinct from the IFN-gamma-dependent mechanism and also suggest that CIITA is not required.
Division of Cardiovascular Medicine, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, CT 06536, USA. mark.collinge@yale.edu
M
M
Collinge
R
R
Pardi
J R
JR
Bender
D000328:Adult; D002448:Cell Adhesion / Q000276:immunology; D018920:Coculture Techniques; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000276:immunology*; D005802:Genes, MHC Class II / Q000276:immunology*; D006684:HLA-DR Antigens / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology; D007694:Killer Cells, Natural / Q000276:immunology*; D016296:Mutagenesis; D009687:Nuclear Proteins; D012333:RNA, Messenger / Q000032:analysis; D015534:Trans-Activators / Q000502:physiology*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D014471:Umbilical Veins
D006684:HLA-DR Antigens; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D007371:Interferon-gamma