Publikation: Dendritic cells up-regulate immunoproteasomes and the proteasome regulator PA28 during maturation
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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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MACAGNO, 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-TBibTex
@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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