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The present study was designed to determine the molecular mechanisms by which 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-κB transcription factors was addressed. The IL-10 effect was investi-gated in a human lymphoblastoid cell system defective for TAP1+2 genes (T2 cell line) and in the 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, suggesting a potential role of TAP1+2 molecules. In the same experimental conditions, the NF-κB activity was unaffected. Instead, after 3 h of exposuretoIL-10, the HLA downmodulation was observed in both cell lines, the NF-κB factors activity being strongly reduced. In addition, the transfection of the inhibitor of NF-κB, IκBa, prevented the IL-10 effect on HLA class I antigen expression in the T3 cell line. This phenomenon was observed after 3 h but not 48 h of IL-10 incubation. These evidences indicate a time dependent involvement of TAP1+2 antigens and of NF-κB activity in the IL-10-induced major histocompatibility complex (MHC) class I downmodulation. [ABSTRACT FROM AUTHOR]