Dendritic cells up-regulate immunoproteasomes and the proteasome regulator PA28 during maturation.
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.
Macagno
A
A
Research Department Cantonal Hospital St. Gall, St. Gallen, Switzerland.
Gilliet
M
M
Sallusto
F
F
Lanzavecchia
A
A
Nestle
F O
FO
Groettrup
M
M
D017951:Antigen Presentation / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D020536:Enzyme Activators / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D009097:Multienzyme Complexes / Q000235:genetics / Q000276:immunology*; D009124:Muscle Proteins; D046988:Proteasome Endopeptidase Complex; D011506:Proteins / Q000235:genetics / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology
D020536:Enzyme Activators; D009097:Multienzyme Complexes; D009124:Muscle Proteins; C085047:PSME1 protein, human; D011506:Proteins; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex