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Expression of housekeeping and immunoproteasome subunit genes is differentially regulated in positively and negatively selecting thymic stroma subsets

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Nil,  Ahmed
Emeritus Group: Molecular Embryology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Firat,  Elke
Georges Köhler Laboratory, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Sobek,  Vera
Emeritus Group: Cellular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Eichmann,  Klaus
Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Niedermann,  Gabriele
Emeritus Group: Cellular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Citation

Nil, A., Firat, E., Sobek, V., Eichmann, K., & Niedermann, G. (2004). Expression of housekeeping and immunoproteasome subunit genes is differentially regulated in positively and negatively selecting thymic stroma subsets. European Journal of Immunology, 34, 2681-2689.


Cite as: http://hdl.handle.net/11858/00-001M-0000-002B-9489-2
Abstract
The expression of housekeeping and/or immunoproteasomes in isolated thymic stroma subsets has so far not been analyzed but may have important consequences for self peptide repertoires presented by MHC class I molecules during positive and negative thymic selection. Here we determined the expression of housekeeping and immunoproteasome β subunits and of PA28 in positively and negatively selecting stroma subsets. Positively selecting cortical thymic epithelial cells (cTEC) expressed only housekeeping but no immunoproteasome β subunit mRNA and proteins. However, immunoproteasome β subunits could be induced in cTEC by infection with Listeria monocytogenes or injection of IFN-γ. In negatively selecting stroma including medullary epithelial cells and dendritic cells, incomplete and low representation of housekeeping β subunit proteins but high and complete expression of immunoproteasome β subunit proteins suggests absence of proper housekeeping proteasomes and predominance of immunoproteasomes. Expression of immunoproteasome β subunits in negatively selecting stroma was independent of IFN-γ receptor as shown in knockout (KO) mice. Absence of LMP2 altered thymic selection of the MHC class I-restricted transgenic P14 TCR in KO mice. The data suggest that negative selection may primarily involve immunoproteasome peptide repertoires and that peripheral infection may influence peptide repertoires involved in positive selection.