Transactivation of Classical and Nonclassical HLA Class I Genes Through the IFN-Stimulated Response Element

• Published in: The Journal of immunology (1950) 1999-08, Vol.163 (3), p.1428-1434
• Main Authors: Gobin, Sam J. P, Zutphen, Marlijn van, Woltman, Andrea M, Elsen, Peter J. van den
• Format: Article
• Language: English
• Subjects: Base Sequence; Binding Sites - genetics; Binding Sites - immunology; Cell Line, Transformed; DNA-Binding Proteins - genetics; DNA-Binding Proteins - immunology; DNA-Binding Proteins - metabolism; Genes, MHC Class I - immunology; Genetic Markers; Humans; Interferon-gamma - pharmacology; Promoter Regions, Genetic - immunology; Protein Binding - genetics; Protein Binding - immunology; Response Elements - immunology; Sp1 Transcription Factor - immunology; Sp1 Transcription Factor - metabolism; Transcription Factors - genetics; Transcription Factors - immunology; Transcription Factors - metabolism; Transcriptional Activation - immunology; Tumor Cells, Cultured; Upstream Stimulatory Factors
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.163.3.1428

The IFN-stimulated response element (ISRE) is an important conserved cis-acting regulatory element in the promoter of MHC class I genes, but displays considerable locus-specific nucleotide variation. In this report, the putative ISREs of classical and nonclassical HLA class I genes were investigated for their contribution to MHC class I transactivation. It is shown that IFN-gamma induced MHC class I transactivation through the ISRE of HLA-A, HLA-B, HLA-C, and HLA-F. This is congruent with the binding of IFN regulatory factor-1 to the ISREs of these loci upon IFN-gamma treatment. Sp1 was shown to bind to the CG-rich sequences in the ISRE regions of HLA-B, HLA-C, and HLA-G. The putative E box 5' of the ISRE in most HLA-B alleles was shown to bind the upstream stimulatory factors (USF) 1 and 2. The Sp1 and USF binding sites did not influence IFN-gamma-induced transactivation. However, the USF binding site played a suppressive role in the constitutive expression of HLA-B. The locus-specific transcriptional control through the ISRE could be an important mechanism in the differential regulation of classical and nonclassical MHC class I expression, which determines adequate Ag presentation upon pathogenic challenge.