Anti-beta-interferon antibodies inhibit the increased expression of HLA-B7 mRNA in tumor necrosis factor-treated human fibroblasts: structural studies of the beta 2 interferon involved.

Recombinant Escherichia coli-derived human tumor necrosis factor (TNF) induces the 1.3-kilobase beta 2 interferon (IFN-beta 2) mRNA in human diploid fibroblasts (FS-4 strain). IFN-beta 2 is serologically related to the well-characterized IFN-beta 1 (respective antisera cross-neutralize the heterologous protein). Polyclonal and monoclonal anti-IFN-beta antibodies inhibit the increase in class I HLA gene expression (HLA-B7 mRNA) in TNF-treated FS-4 cells suggesting that TNF-induced IFN-beta 2 mediates the enhancing effect of TNF on HLA gene expression in human fibroblasts. The structure of this autocrine human interferon has been determined. A cDNA library was prepared from polyadenylylated RNA extracted from TNF-induced FS-4 cells, and eight IFN-beta 2 cDNA clones were isolated using a 21-nucleotide synthetic oligonucleotide probe. The 1128-nucleotide sequence of IFN-beta 2 mRNA and the 212-amino acid sequence of the IFN-beta 2 protein were deduced from these cDNA clones. The amino acid sequences of the serologically related human IFN-beta 1 and -beta 2 were compared using the Sellers TT metric algorithm for locating similarities and using the pattern scoring method for evaluating the observed similarities. IFN-beta 1 and -beta 2 each contain a segment that is approximately 100 amino acids including 39 amino acids that are aligned and identical in the two proteins. The hydropathic index plots across these segments in the two proteins are also strikingly similar. The region of similarity between IFN-beta 1 and -beta 2 includes a section that is also highly conserved in all IFN-alpha species sequenced. Thus IFN-beta 2 shares structural similarities with other human interferons that also preferentially increase class I HLA gene expression.