Differential expression of constitutive and inducible proteasome subunits in human monocyte-derived DC differentiated in the presence of IFN-alpha or IL-4

Several studies strongly suggest that DC differentiated in vitro in the presence of type I IFN acquire more potent immune stimulatory properties, compared with DC differentiated in vitro with IL-4. However, little is known about the molecular mechanisms underlying this phenomenon. To address this question, we compared the Ag-processing machinery (APM) profile in human DC grown in the presence of IFN-α (IFNDC) or IL-4 (IL-4DC). Using a panel of APM component-specific mAb in Western blot experiments, we found that IFNDC preferentially express inducible proteasome subunits (LMP2, LMP7, and MECL1) both at immature and mature stages. In contrast, immature IL-4DC co-express both constitutive (β1, β2, and β5) and inducible subunits, as shown by Western blotting analysis. In addition, immature IFNDC express higher levels of TAP1, TAP2, calnexin, calreticulin, tapasin, and HLA class I molecules than IL-4DC. The different proteasome profiles of IFNDC and IL-4DC were associated with a greater ability of IFNDC to present an immunodominant epitope that requires LMP7 expression for its processing. In general, these data show the impact of cytokines on APM component expression and hence the Ag-processing ability of DC.