Different interactions of interferon-alpha subtypes at the surface of epithelial and lymphoid cells.
The interaction of different interferon (IFN)-alpha subtypes with different cell types was investigated using a unique monoclonal antibody (MAb), I-4-A. This MAb reacts in immunoassays equally with IFN-alpha 2b and IFN-alpha 4a, but does not inhibit the binding of IFN to cell receptors. 125I-labeled I-4-A reacted with IFN-alpha 4a and IFN-alpha 2b bound to receptors on Daudi cells. However, in a "double assay" developed using Daudi cells to measure antiviral and antiproliferative activity, I-4-A neutralized both activities of IFN-alpha 4a, but neither of IFN-alpha 2b. Similarly, in studies on the activation of natural killer (NK) cells, I-4-A neutralized the effect of IFN-alpha 4a but not that of IFN-alpha 2b. In contrast, when cell lines other than lymphoid were studied, e.g., HEp 2 and WISH cells, I-4-A neutralized the antiviral activity of both IFN-alpha subtypes. The neutralization of one IFN-alpha subtype but not another on lymphoid cells suggests a difference either in the receptor-bound form of the subtypes, or in subsequent interactions prerequisite for activation of these cells. Furthermore, the neutralization of a particular IFN subtype, alpha 2b, on epithelial-derived but not lymphoid cells suggests differences in the IFN-receptor complex or the mechanisms of cell activation between these cell types. An implication from these studies is that some IFN-alpha subtypes can exert different functions on lymphoid and epithelial cells.
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ML
Centre for Molecular Biology and Medicine, Monash University, Clayton, Victoria, Australia.
Chambers
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P
Hertzog
P J
PJ
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D000937:Antigen-Antibody Reactions / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D007370:Interferon Type I / Q000276:immunology / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology; D008214:Lymphocytes / Q000378:metabolism*; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D017471:Receptors, Interferon / Q000378:metabolism; D011994:Recombinant Proteins; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D007370:Interferon Type I; D017471:Receptors, Interferon; D011994:Recombinant Proteins