Article: article from journal or magazin.
Dendritic cells up-regulate immunoproteasomes and the proteasome regulator PA28 during maturation.
European Journal of Immunology
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
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.
Antigen Presentation/immunology, Cell Differentiation/immunology, Cells, Cultured, Cysteine Endopeptidases/genetics, Cysteine Endopeptidases/immunology, Dendritic Cells/cytology, Dendritic Cells/immunology, Enzyme Activators/immunology, Gene Expression Regulation/immunology, Humans, Multienzyme Complexes/genetics, Multienzyme Complexes/immunology, Muscle Proteins, Proteasome Endopeptidase Complex, Proteins/genetics, Proteins/immunology, Up-Regulation/immunology
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