Maturation pathways of dendritic cells determine TAP1 and TAP2 levels and cross‐presenting function

Abstract

Cross‐presentation of exogenous antigens in the HLA class I pathway is key to the antigen presenting function of mature tumor‐loaded dendritic cells (DC). Conditions of DC maturation have been shown to influence the ability of DCs to induce T cell effector functions. However, it remains unknown if different pathways of DC maturation are associated with modulation in the ability of DCs to cross‐present tumor‐associated antigens. We compared DC matured with three clinically relevant cytokine protocols: IL‐1β, TNF‐α, IL‐6 (DC‐0), DC‐0+PGE‐2, or IFN‐γ, IFN‐α, TNF‐α, and IL1‐β (DC‐1). We found that these DC vary in the ability to cross‐present tumor antigens to CTL, with DC‐1 protocol being significantly more effective than the other protocols. This level of TA cross presentation was correlated with the level of expression of the antigen processing machinery (APM) components, TAP1 and TAP2, and to a lesser extent, tapasin, indicating that these components could be used to standardize DC preparations for optimal function. However, upregulation of TAP1/2 was not sufficient to explain the strongest cross‐presentation ability induced by DC‐1 cells, since IFN‐γ did not generate DC as effective at cross‐presentation as the full DC‐1 cytokine cocktail. These data indicate that DC maturation pathways modulate APM component expression and that DC vary in the ability to cross‐present TA to HLA class I‐restricted CTL.