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Lack of MHC-II expression in activated mouse T cells correlates with DNA methylation at the CIITA-PIII region

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Abstract

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.

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Abbreviations

CIITA:

Class II transactivator

CIITA-PIII:

CIITA promoter III

5-AZA-dC:

5′-AZA-2′-deoxycytidine

References

  • Chang CH, Hong SC, Hughes CC, Janeway CA Jr, Flavell RA (1995) CIITA activates the expression of MHC class II genes in mouse T cells. Int Immunol 7:1515–1518

    Article  PubMed  CAS  Google Scholar 

  • Holling TM, van der Stoep N, Quinten E, van den Elsen PJ (2002) Activated human T cells accomplish MHC class II expression through T cell-specific occupation of class II transactivator promoter III. J Immunol 168:763–770

    PubMed  CAS  Google Scholar 

  • Holling TM, Schooten E, Langerak AW, van den Elsen PJ (2004) Regulation of MHC class II expression in human T-cell malignancies. Blood 103:1438–1444

    Article  PubMed  CAS  Google Scholar 

  • Keshet I, Lieman-Hurwitz J, Cedar H (1986) DNA methylation affects the formation of active chromatin. Cell 44:535–543

    Article  PubMed  CAS  Google Scholar 

  • Ko HS, Fu SM, Winchester RJ, Yu DT, Kunkel HG (1979) Ia determinants on stimulated human T lymphocytes. Occurrence on mitogen- and antigen-activated T cells. J Exp Med 150:246–255

    Article  PubMed  CAS  Google Scholar 

  • Muhlethaler-Mottet A, Otten LA, Steimle V, Mach B (1997) Expression of MHC class II molecules in different cellular and functional compartments is controlled by differential usage of multiple promoters of the transactivator CIITA. EMBO J 16:2851–2860

    Article  PubMed  CAS  Google Scholar 

  • Muhlethaler-Mottet A, Di Berardino W, Otten LA, Mach B (1998) Activation of the MHC class II transactivator CIITA by interferon-gamma requires cooperative interaction between Stat1 and USF-1. Immunity 8:157–166

    Article  PubMed  CAS  Google Scholar 

  • Otten LA, Tacchini-Cottier F, Lohoff M, Annunziato F, Cosmi L, Scarpellino L, Louis J, Steimle V, Reith W, Acha-Orbea H (2003) Deregulated MHC class II transactivator expression leads to a strong Th2 bias in CD4+ T lymphocytes. J Immunol 170:1150–1157

    PubMed  CAS  Google Scholar 

  • Piskurich JF, Wang Y, Linhoff MW, White LC, Ting JP (1998) Identification of distinct regions of 5′ flanking DNA that mediate constitutive, IFN-gamma, STAT1, and TGF-beta-regulated expression of the class II transactivator gene. J Immunol 160:233–240

    PubMed  CAS  Google Scholar 

  • van den Elsen PJ, van der Stoep N, Viëtor HE, Wilson E, van Zutphen M, Gobin SJP (2000) Lack of CIITA expression is central to the absence of antigen presentation functions of trophoblasts cells and is caused by methylation of the IFNg inducible promoter (PIV) of CIITA. Hum Immunol 61:850–862

    Article  PubMed  Google Scholar 

  • van der Stoep N, Quinten E, van den Elsen PJ (2002) Transcriptional regulation of the MHC class II trans-activator (CIITA) promoter III: identification of a novel regulatory region in the 5′-untranslated region and an important role for cAMP-responsive element binding protein 1 and activating transcription factor-1 in CIITA-promoter III transcriptional activation in B lymphocytes. J Immunol 169: 5061–5071

    PubMed  Google Scholar 

  • Waldburger JM, Rossi S, Hollander GA, Rodewald HR, Reith W, Acha-Orbea H (2003) Promoter IV of the class II transactivator gene is essential for positive selection of CD4+ T cells. Blood 101:3550–3559

    Article  PubMed  CAS  Google Scholar 

  • Wong AW, Ghosh N, McKinnon KP, Reed W, Piskurich JF, Wright KL, Ting JP (2002) Regulation and specificity of MHC2TA promoter usage in human primary T lymphocytes and cell line. J Immunol 169:3112–3119

    PubMed  CAS  Google Scholar 

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Acknowledgements

This research is supported by the Dutch Cancer Society (grants 98-1732 and 03-2798 to PvdE) and a Leiden University Medical Center research development grant.

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Correspondence to Tjadine M. Holling.

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Schooten, E., Klous, P., van den Elsen, P.J. et al. Lack of MHC-II expression in activated mouse T cells correlates with DNA methylation at the CIITA-PIII region. Immunogenetics 57, 795–799 (2005). https://doi.org/10.1007/s00251-005-0051-8

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  • DOI: https://doi.org/10.1007/s00251-005-0051-8

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