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CIITA promoter I CARD-deficient mice express functional MHC class II genes in myeloid and lymphoid compartments

Genes & Immunity volume 13, pages 299–310 (2012)Cite this article

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Abstract

Three distinct promoters control the master regulator of major histocompatibility complex (MHC) class II expression, class II transactivator (CIITA), in a cell type-specific manner. Promoter I (pI) CIITA, expressed primarily by dendritic cells (DCs) and macrophages, expresses a unique isoform that contains a caspase-recruitment domain (CARD). The activity and function of this isoform are not understood, but are believed to enhance the function of CIITA in antigen-presenting cells. To determine whether isoform I of CIITA has specific functions, CIITA mutant mice were created in which isoform I was replaced with isoform III sequences. Mice in which pI and the CARD-encoding exon were deleted were also created. No defect in the formation of CD4 T cells, the ability to respond to a model antigen or bacterial or viral challenge was observed in mice lacking CIITA isoform I. Although CIITA and MHC-II expression was decreased in splenic DCs, pI knockout animals expressed CIITA from downstream promoters, suggesting that control of pI activity is mediated by unknown distal elements that could act at pIII, the B-cell promoter. Thus, no critical function is linked to the CARD domain of CIITA isoform I with respect to basic immune system development, function and challenge.

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Acknowledgements

We thank Dr Joseph Sabatino for help with some of the experiments presented. We also thank the Emory University School of Medicine Core Facility for Flow Cytometry and the NIH tetramer core. This study was supported by the National Institutes of Health grants RO1AI43000 and R56AI34000 (to JMB), PO1 AI080192-01 (to JMB and RA), HHSN266 200700006CMD8 (to IS) and the American Cancer Society postdoctoral fellowship PF-09-134-01-MPC (to BY).

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  1. Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, USA

    W M Zinzow-Kramer, B A Youngblood, K M Rosenthal, R Butler, I Skountzou, R Ahmed, B D Evavold & J M Boss

  2. Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA

    A B Long

  3. Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA

    B A Youngblood, A-U-R Mohammed, I Skountzou, R Ahmed & J M Boss

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  1. W M Zinzow-Kramer
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Zinzow-Kramer, W., Long, A., Youngblood, B. et al. CIITA promoter I CARD-deficient mice express functional MHC class II genes in myeloid and lymphoid compartments. Genes Immun 13, 299–310 (2012). https://doi.org/10.1038/gene.2011.86

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