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The genes of the transporter associated with antigen processing (Tap)-1, and the low molecular weight peptide (Lmp)-2, are crucial for class I major histocompatibility complex function and share a common bidirectional promoter. In murine bone marrow-derived macrophages, interferon gamma (IFN-g) induced Tap-1 and upregulated Lmp-2, which is constitutively expressed at low levels. The IFN-g-induction was independent of early gene synthesis. The mRNA induced by IFN-g was very stable. In macrophages from STAT1 knockout mice, IFN-g did not induce the expression of Tap-1 or Lmp-2. Several areas in the promoter can be controlled by IFN-g, such as proximal and distal GAS boxes in the direction of the Tap-1 gene, NFgB and IRF-1 boxes. By making deletions of the promoter, we found that only the proximal GAS and IRF-1 boxes are required for IFN-g induction of Tap-1 and Lmp-2. Experiments using nuclear extracts from macrophages treated for 30 min with IFN-g and gel shift analysis indicated that STAT1 binds to the GAS box. The nuclear extracts from macrophages treated for at least 2 h with IFN-g bound to the IRF-1 box. These results indicate that both STAT1 and IRF-1 are required for the IFN-g induction of Tap-1 and Lmp-2 genes.

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