COX‐1 inhibitors block MHC‐restricted exogenous antigen presentation in dendritic cells

Abstract

T lymphocytes recognize antigens in the form of short peptides presented by MHC molecules. Although MHC‐restricted antigen presentation is an essential process for the initiation T cell responses, it has received little attention as a target of therapeutic immunomodulation. In an effort to search for and characterize MHC‐restricted antigen presentation modulators, we screened several thousands of compounds for their ability to inhibit or enhance exogenous antigen presentation in dendritic cells (DCs). We found that COX‐1 inhibitors, aspirin and ibuprofen, efficiently block MHC‐restricted presentation of an exogenous antigen, ovalbumin (OVA), when added to cultures of DC2.4 cells and BM‐DCs for 18 h or longer. The antigen presentation inhibitory activity of ibuprofen was much more potent than aspirin. The COX‐1 inhibitors, however, did not affect phagocytic activity, the expression level of total MHC molecules and co‐stimulatory molecules in DCs. DCs differentiated from BM cells in the presence of COX‐1 inhibitors were also suppressed in the antigen presentation capability, and this suppressive activity was more prominent when developing DCs were exposed with the COX‐1 inhibitors at the early stage of maturation. These results suggest that prolonged administration of COX‐1 inhibitors may impair antigen presentation capability of DCs.