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Immunoproteasomes largely replace constitutive proteasomes during an antiviral and antibacterial immune response in the liver

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2001

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Khan, Selina
Broek, Marlies van den
Schwarz, Katrin
Giuli, Rita de
Diener, Pierre-André

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The Journal of Immunology. 2001, 167(12), pp. 6859-6868. ISSN 0022-1767. eISSN 1550-6606. Available under: doi: 10.4049/jimmunol.167.12.6859

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The proteasome is critically involved in the production of MHC class I-restricted T cell epitopes. Proteasome activity and epitope production are altered by IFN-gamma treatment, which leads to a gradual replacement of constitutive proteasomes by immunoproteasomes in vitro. However, a quantitative analysis of changes in the steady state subunit composition of proteasomes during an immune response against viruses or bacteria in vivo has not been reported. Here we show that the infection of mice with lymphocytic choriomeningitis virus or Listeria monocytogenes leads to an almost complete replacement of constitutive proteasomes by immunoproteasomes in the liver within 7 days. Proteasome replacements were markedly reduced in IFN-gamma(-/-) mice, but were only slightly affected in IFN-alphaR(-/-) and perforin(-/-) mice. The proteasome regulator PA28alpha/beta was up-regulated, whereas PA28gamma was reduced in the liver of lymphocytic choriomeningitis virus-infected mice. Proteasome replacements in the liver strongly altered proteasome activity and were unexpected to this extent, since an in vivo half-life of 12 days had been previously assigned to constitutive proteasomes in the liver. Our results suggest that during the peak phase of viral and bacterial elimination the antiviral cytotoxic T lymphocyte response is directed mainly to immunoproteasome-dependent T cell epitopes, which would be a novel parameter for the design of vaccines.

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570 Biowissenschaften, Biologie

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ISO 690KHAN, Selina, Marlies van den BROEK, Katrin SCHWARZ, Rita de GIULI, Pierre-André DIENER, Marcus GRÖTTRUP, 2001. Immunoproteasomes largely replace constitutive proteasomes during an antiviral and antibacterial immune response in the liver. In: The Journal of Immunology. 2001, 167(12), pp. 6859-6868. ISSN 0022-1767. eISSN 1550-6606. Available under: doi: 10.4049/jimmunol.167.12.6859
BibTex
@article{Khan2001Immun-22141,
  year={2001},
  doi={10.4049/jimmunol.167.12.6859},
  title={Immunoproteasomes largely replace constitutive proteasomes during an antiviral and antibacterial immune response in the liver},
  number={12},
  volume={167},
  issn={0022-1767},
  journal={The Journal of Immunology},
  pages={6859--6868},
  author={Khan, Selina and Broek, Marlies van den and Schwarz, Katrin and Giuli, Rita de and Diener, Pierre-André and Gröttrup, Marcus}
}
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