Differential regulation of HLA class I genes by interferon.
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 inducible 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 transcription 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.
Med. Universitätsklinik und Poliklinik, Abt II, Tübingen, Federal Republic of Germany.
H
H
Schmidt
V
V
Gekeler
H
H
Haas
G
G
Engler-Blum
I
I
Steiert
H
H
Probst
C A
CA
Müller
D000483:Alleles; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002460:Cell Line; D002872:Chromosome Deletion; D005786:Gene Expression Regulation / Q000187:drug effects*; D005802:Genes, MHC Class II; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D007372:Interferons / Q000494:pharmacology*; D007739:L Cells; D051379:Mice; D008969:Molecular Sequence Data; D014162:Transfection
D015395:Histocompatibility Antigens Class I; D007372:Interferons