Expression of MHC II Genes
Innate and adaptive immunity are connected via antigen processing and presentation (APP), which results in the presentation of antigenic peptides to T cells in the complex with the major histocompatibility (MHC) determinants. MHC class II (MHC II) determinants present antigens to CD4+ T cells, which are the main regulators of the immune response. Their genes are transcribed from compact promoters that form first the MHC II enhanceosome, which contains DNA-bound activators and then the MHC II transcriptosome with the addition of the class II transactivator (CIITA). CIITA is the master regulator of MHC II transcription. It is expressed constitutively in dendritic cells (DC) and mature B cells and is inducible in most other cell types. Three isoforms of CIITA exist, depending on cell type and inducing signals. CIITA is regulated at the levels of transcription and post-translational modifications, which are still not very clear. Inappropriate immune responses are found in several diseases, including cancer and autoimmunity. Since CIITA regulates the expression of MHC II genes, it is involved directly in the regulation of the immune response. The knowledge of CIITA will facilitate the manipulation of the immune response and might contribute to the treatment of these diseases.
KeywordsHuman Leukocyte Antigen Locus Control Region Bare Lymphocyte Syndrome Proximal Promoter Sequence Transactivator CIITA
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- Hake SB, Masternak K, Kammerbauer C, Janzen C, Reith W, Steimle V (2000) CIITA leucine-rich repeats control nuclear localization, in vivo recruitment to the major histocompatibility complex (MHC) class II enhanceosome MHC class II gene transactivation. Mol Cell Biol 20:7716–7725PubMedCrossRefGoogle Scholar
- Landmann S, Muhlethaler-Mottet A, Bernasconi L, Suter T, Waldburger JM, Masternak K, Arrighi JF, Hauser C, Fontana A, Reith W (2001) Maturation of dendritic cells is accompanied by rapid transcriptional silencing of class II transactivator (CIITA) expression. J Exp Med 194:379–391PubMedCrossRefGoogle Scholar
- Li G, Harton JA, Zhu X, Ting JP (2001) Downregulation of CIITA function by protein kinase a (PKA)-mediated phosphorylation: mechanism of prostaglandin E, cyclic AMP, PKA inhibition of class II major histocompatibility complex expression in monocytic lines. Mol Cell Biol 21:4626–4635PubMedCrossRefGoogle Scholar
- Van den Elsen PJ, van der Stoep N, Vietor HE, Wilson L, van Zutphen M, Gobin SJ (2000) 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. Hum Immunol 61:850–862PubMedCrossRefGoogle Scholar