We examined the proposed role of human chromosome 21 in determining the cellular sensitivity to human α, β, and γ interferions (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 of 125I-labeled HuIFN-α2 (125I-HuIFn-α2), which was not observed with mouse parent (A9) cells. Crosslinking of 125I-HuIFN-α2 bound to WA17 cells with disuccinimidyl suberate yielded a complex of M(r) ~ 150,000 similar to the 125I-labeled-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 the 125I-HuIFN-α2-receptor complex obtained from human cells but not free 125I-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.
|Number of pages||5|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|Issue number||17 I|
|State||Published - 1984|