Bipartite regulation of different components of the MHC class I antigen-processing machinery during dendritic cell maturation

Dendritic cells (DC) are professional antigen-presenting cells (APC) which proceed from immature to a mature stage during their final differentiation. Immature DC are highly effective in terms of antigen uptake and processing , whereas mature DC become potent immunostimulatory cells. Until now, the e xpression profiles of the major components of the MHC class I antigen-proce ssing machinery (APM) during DC development have not been well characterize d. In this study, the mRNA and protein expression levels of the IFN-gamma i nducible proteasome subunits, of the proteasome activators PA28, and of key components required for peptide transport and MHC class I-peptide complex assembly have been evaluated in immature and mature stages of human monocyt e-derived DC using semiquantitative RT-PCR and Western blot analyses. The I FN-gamma -responsive immunoproteasome subunits LMP2, LMP7 and MECL1 are up- regulated in immature DC, whereas the other components of the MHC class I p resentation machinery, such as PA28, TAP, tapasin, and HLA heavy and light chains, were found to be more abundant in mature DC. These findings support the hypothesis that immature DC produced by the differentiation of monocyt es in response to IL-4 and granulocyte macrophage colony stimulating factor first increase their capacity to capture antigens and process them into pe ptides, thereby switching from housekeeping to immunoproteasomes, while mat ure DC rather up-regulate the components required for peptide translocation and MHC class I-peptide complex formation, and thus specialize in antigen presentation. Our results establish that MHC class I, like MHC class II sur face expression, is markedly regulated during DC development and maturation .