Differential expression of constitutive and inducible proteasome subunits in human monocyte-derived DC differentiated in the presence of IFN-α 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.