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Dendritic cells up-regulate immunoproteasomes and the proteasome regulator PA28 during maturation

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1999

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Macagno, Annalisa
Gilliet, Michel
Sallusto, Federica
Lanzavecchia, Antonio
Nestle, Frank O.

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European Journal of Immunology. 1999, 29(12), pp. 4037-4042. ISSN 0014-2980. eISSN 1521-4141. Available under: doi: 10.1002/(SICI)1521-4141(199912)29:12<4037::AID-IMMU4037>3.0.CO;2-T

Zusammenfassung

Dendritic cells (DC) are highly specialized professional antigen presenting cells which are pivotal for the initiation and control of the cytotoxic T cell response. Upon stimulation by cytokines, bacteria, or CD40L DC undergo a maturation process from an antigen-receptive state to a state of optimal stimulation of T cells. We investigated the composition of proteasomes of DC derived from human peripheral blood monocytes before and after stimulation by CD40L, LPS, or proinflammatory cytokines (TNF-alpha + IL-6 + IL-1beta). Immunoprecipitation of proteasomes and analysis on two-dimensional gels revealed that during maturation the inducible proteasome subunits LMP2, LMP7, and MECL-1 are up-regulated and that the neosynthesis of proteasomes is switched exclusively to the production of immunoproteasomes containing these subunits. The proteasome regulator PA28 is markedly up-regulated in mature DC and in addition a so - far unidentified 21-kDa protein co-precipitates with the proteasome in LPS - stimulated DC. These changes in proteasome composition may be functionally linked to special properties of DC like MHC class I up-regulation or cross-priming. Our findings imply that the spectrum of class I-bound peptides may change after DC maturation which could be relevant for the design of DC - based vaccines.

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570 Biowissenschaften, Biologie

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Antigen presentation, TNF- alpha, CD40, Lipopolysaccharide, LMP2

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ISO 690MACAGNO, Annalisa, Michel GILLIET, Federica SALLUSTO, Antonio LANZAVECCHIA, Frank O. NESTLE, Marcus GRÖTTRUP, 1999. Dendritic cells up-regulate immunoproteasomes and the proteasome regulator PA28 during maturation. In: European Journal of Immunology. 1999, 29(12), pp. 4037-4042. ISSN 0014-2980. eISSN 1521-4141. Available under: doi: 10.1002/(SICI)1521-4141(199912)29:12<4037::AID-IMMU4037>3.0.CO;2-T
BibTex
@article{Macagno1999Dendr-22233,
  year={1999},
  doi={10.1002/(SICI)1521-4141(199912)29:12<4037::AID-IMMU4037>3.0.CO;2-T},
  title={Dendritic cells up-regulate immunoproteasomes and the proteasome regulator PA28 during maturation},
  number={12},
  volume={29},
  issn={0014-2980},
  journal={European Journal of Immunology},
  pages={4037--4042},
  author={Macagno, Annalisa and Gilliet, Michel and Sallusto, Federica and Lanzavecchia, Antonio and Nestle, Frank O. and Gröttrup, Marcus}
}
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