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The Journal of Immunology, 1998, 161: 2276-2283.
Copyright © 1998 by The American Association of Immunologists

The Role of Enhancer A in the Locus-Specific Transactivation of Classical and Nonclassical HLA Class I Genes by Nuclear Factor {kappa}B1

Sam J. P. Gobin2, Vivian Keijsers, Marlijn van Zutphen and Peter J. van den Elsen

Department of Immunohematology and Blood Bank, Leiden University Medical Center, Leiden, The Netherlands

HLA class I expression is tightly controlled at the transcriptional level by several conserved regulatory elements in the proximal promoter region. In this study, the two putative {kappa}B motifs of enhancer A ({kappa}B1 and {kappa}B2) of the classical and nonclassical HLA class I genes were investigated for their binding properties of transcription factors and tested for their contribution to the NF-{kappa}B-induced route of transactivation. It was shown that NF-{kappa}B-induced transactivation through enhancer A is most important for the HLA-A locus, which contains two NF-{kappa}B binding sites. Although the enhancer A of HLA-B contains only one NF-{kappa}B binding site ({kappa}B1), there was still a moderate transactivation by NF-{kappa}B. Since HLA-F, which also possesses one NF-{kappa}B binding site but lacks protein binding to its {kappa}B2 site, was not transactivated by NF-{kappa}B, the NF-{kappa}B-mediated transactivation through the {kappa}B1 motif in HLA-B is most probably facilitated by binding of the transcription factor Sp1 to the upstream {kappa}B2 site. Thus, transcriptional regulation of HLA class I genes by NF-{kappa}B is restricted to the HLA-A and HLA-B loci.




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