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Differential regulation of HLA class I genes by interferon

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Abstract

Allele-specific differences in the regulation of HLA class I genes by type I interferon (IFN) were observed after transfection of eight HLA-B,-A, or-C genes into mouse L cells. HLA-B7 and -Bw64 gene expression was significantly more inductible by type I IFN than the genes coding for HLA-B27, HLA-B51, HLA-B38, HLA-B39, HLA-Cw3, and HLA-A2 antigens. Modification of the 5′ end of HLA-B7 and HLA-B27 genes revealed the presence of enhancer sequences responding to IFN treatment in the 5′ untranslated region of HLA-B7, but not of HLA-B27 and suggested further, independently acting enhancer elements downstream of the transciption initiation site. Comparison of 5′ enhancer region sequences in correlation with type I IFN inducibility of the different HLA class I alleles indicated that the exchange of only two nucleotides in the interferon response sequence (IRS) or enhancer A region of HLA-B7 or -Bw64 could account for nonregulated promoters in all other HLA-A,-B or -C alleles analyzed. Thus, type I IFN stimulation of HLA class I genes in mouse L cells appears to predominantly operate in most alleles by a mechanism targeted to enhancer sequences downstream of the gene's transcription initiation site.

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Authors and Affiliations

  1. Med. Universitätsklinik und Poliklinik, Abt. II, D-7400, Tübingen, Federal Republic of Germany

    H. Schmidt, G. Engler-Blum & I. Steiert

  2. Institut für Physiologische Chemie, D-7400, Tübingen, Federal Republic of Germany

    V. Gekeler, H. Haas, H. Probst & C. A. Müller

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  1. H. Schmidt
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  2. V. Gekeler
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  3. H. Haas
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  4. G. Engler-Blum
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  5. I. Steiert
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  6. H. Probst
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  7. C. A. Müller
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Schmidt, H., Gekeler, V., Haas, H. et al. Differential regulation of HLA class I genes by interferon. Immunogenetics 31, 245–252 (1990). https://doi.org/10.1007/BF00204896

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  • DOI: https://doi.org/10.1007/BF00204896

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