Lack of MHC-II expression in activated mouse T cells correlates with DNA methylation at the CIITA-PIII region.
In contrast to activated human T cells, activated mouse T cells fail to express MHC class II molecules (MHC-II) at their cell surface. This is because mouse T cells hardly produce mRNA encoding the MHC-II molecules I-A and I-E, due to severely impaired expression levels upon T-cell activation of the mhc2ta gene, encoding the class II transactivator (CIITA). In humans, activated T cells express exclusively the CIITA promoter III (CIITA-PIII) isoform, which results in cell surface expression of all MHC-II isotypes (HLA-DR, -DP and -DQ). In this study, we demonstrate that methylation of CIITA-PIII contributes to the failure of mouse T cells to transcribe the mhc2ta and the resulting I-A/E genes, explaining the lack of I-A/E molecule expression at the cell surface following activation.
Schooten
Erik
E
Division of Molecular Biology, Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, E3-Q, Albinusdreef 2, 2333, ZA Leiden, The Netherlands.
Klous
Petra
P
van den Elsen
Peter J
PJ
Holling
Tjadine M
TM
D000818:Animals; D002460:Cell Line; D019175:DNA Methylation; D005786:Gene Expression Regulation; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics* / Q000276:immunology
D000949:Histocompatibility Antigens Class II; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators