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.