Receptors for Human α and β Interferon but not for γ Interferon are Specified by Human Chromosome 21

• Published in: Proceedings of the National Academy of Sciences - PNAS 1984-09, Vol.81 (17), p.5504-5508
• Main Authors: Raziuddin, Arati, Sarkar, Fazlul H., Dutkowski, Regina, Shulman, Lester, Ruddle, Frank H., Gupta, Sohan L.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Burkitt Lymphoma; Cell growth; Cell Line; Cell lines; Chromosomes; Chromosomes, Human, 21-22 and Y; Crosslinking; Escherichia coli - genetics; Human chromosomes; Humans; Hybrid cells; Hybrid Cells - cytology; Interferon Type I - genetics; Interferon Type I - metabolism; Interferon-gamma - genetics; Interferon-gamma - metabolism; Interferons; Interferons - metabolism; Kinetics; Mice; Receptors; Receptors, Cell Surface - genetics; Receptors, Interferon; Somatic cells
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.81.17.5504

We examined the proposed role of human chromosome 21 in determining the cellular sensitivity to human α , β , and γ interferons (HuIFN-α , -β , and -γ ) and the expression of the receptors for the HuIFNs with the use of mouse--human hybrid cells containing human chromosome 21. Hybrid cells (WA17) containing three copies of human chromosome 21 showed specific displaceable binding of125I-labeled HuIFN-α2(125I-HuIFN-α2), which was not observed with mouse parent (A9) cells. Crosslinking of125I-HuIFNα2bound to WA17 cells with disuccinimidyl suberate yielded a complex of Mr≈ 150,000 similar to the125I-HuIFN-α2-receptor complex obtained with human cells as described earlier. Such a complex was not obtained with mouse parent (A9) cells or with hybrid cells containing certain other human chromosomes but not chromosome 21. Mice inoculated with mouse--human hybrid cells containing human chromosome 21 produce antibodies that block the antiviral action of HuIFN-α and -β on human cells. Such antibodies could immunoprecipitate the125I-HuIFN-α2-receptor complex obtained from human cells but not free125I-HuIFN-α2, indicating that these antibodies were directed against the receptor. WA17 hybrid cells were highly sensitive to the antiviral action of HuIFN-α2, -α (Le) and -β but were completely insensitive to HuIFN-γ . Furthermore,125I-HuIFN-γ showed specific binding to human WISH cells but not to WA17 hybrid cells or A9 mouse cells. The results indicate that the receptors for HuIFN-α and -β but not for HuIFN-γ are specified by human chromosome 21. Hybrid cells containing one, two, or three copies of human chromosome 21 were found to be increasingly sensitive to HuIFN-α2, indicating that a chromosome 21-specified component (possibly the HuIFN-α receptor) may be a limiting factor in the cellular sensitivity to HuIFN-α .