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pubmed:abstractText |
The human interferon-gamma receptor (hIFN-gamma R) extracellular domain interacts in a species-specific manner with both its ligand and an accessory factor encoded on human chromosome 21. Mutant interferon-gamma receptors were constructed by homolog-scanning mutagenesis, replacing segments of the human extracellular domain with the corresponding murine sequence. Replacement of hIFN-gamma R amino acids 1-100, 100-132, 134-183, or 183-245 abolished binding to human interferon-gamma (hIFN-gamma). However, replacement of hIFN-gamma R amino acids 134-209, 183-209, 134-153, 153-167, or 167-183 or deletion of residues 156-165 affected hIFN-gamma binding only partially or not at all. Receptors that bound hIFN-gamma were tested for their ability to signal a functional response, induction of major histocompatibility complex class I antigen expression. Replacement of residues 134-209 greatly reduced the ability of the receptor to signal. This signaling defect could not be attributed solely to a reduction in affinity for ligand and could not be localized to any subregion.
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