HLA class I antigen downregulation by interleukin (IL)-10 is predominantlygoverned by NF-kappa B in the short term and by TAP1+2 in the long term

The present study was designed to determine the molecular mechanisms by whi ch interleukin (IL)-10 prevents the HLA. class I antigen expression at the cell surface. In this context, the potential role of transporter associated with antigen presentation 1+2 (TAP1+2) molecules and NF-kappa B transcript ion factors was addressed, The IL-10 effect was investigated in a human lym phoblastoid cell system defective for TAP1+2 genes (T2 cell line) and in th e related TAP1+2 transfectants (T3 cell line). In this experimental system, after 48 h of incubation in the presence of IL-10, the HLA class I antigen downmodulation was observed in the T3 but not in the T2 cell line, suggest ing a potential role of TAP1+2 molecules. In the same experimental conditio ns, the NF-kappa B activity was unaffected. Instead, after 3 h of exposure to IL-10, the HLA downmodulation was observed in both cell lines, the NF-ka ppa B factors activity being strongly reduced, In addition, the transfectio n of the inhibitor of NF-kappa B, I kappa B alpha, prevented the IL-10 effe ct on HLA class I antigen expression in the T3 cell line. This phenomenon w as observed after 3 h but not 48 h of IL-10 incubation, These evidences ind icate a time dependent involvement of TAP1+2 antigens and of NF-kappa B act ivity in the IL-10-induced major histocompatibility complex (MHC) class I d ownmodulation.