The EBV IL-10 homologue is a selective agonist with impaired binding to the IL-10 receptor
Copyright policy )The EBV IL-10 homologue is a selective agonist with impaired binding to the IL-10 receptor
Abstract BCRF1 is an EBV homologue of human IL-10 (hIL-10) and is known as viral IL-10 (vIL-10). As found earlier for the effects of vIL-10 on mouse mast cells and CD4+ T cells, the efficiency of inhibition by vIL-10 of IL-2 production by human CD4+ T cell clones is approximately 1000-fold diminished compared with hIL-10. We studied the interaction of vIL-10 and an epitope-tagged homologue, vIL-10His6, with recombinant mouse and human IL-10 receptors (mIL-10R, hIL-10R). vIL-10His6 has approximately 1000-fold lower affinity for recombinant IL-10R than does hIL-10, yet stimulates proliferation of mouse Ba/F3 (BaF)-mIL-10R- and human TF1-hIL-10R-transfected cells with a sp. act. comparable to or greater than that of the cellular cytokine. In contrast, BaF-hIL-10R cells are approximately 1000-fold less sensitive to vIL-10His6 than are BaF-mIL-10R cells. An anti-hIL-10R mAb (3F9) blocks responses to both hIL-10 and vIL-10His6, while a soluble form of hIL-10R effectively neutralizes biologic responses only to hIL-10 by both BaF-IL-10R transfectants and normal human peripheral blood cells. The results indicate that biologic responses to both hIL-10 and vIL-10 require the known IL-10R, and suggest the existence of at least one additional IL-10R subunit. We suggest that vIL-10 is a selective agonist that is impaired in its ability to bind the defined IL-10R, which we now designate as IL-10R α.
Herpesvirus 4, Human, Antibodies, Monoclonal, Receptors, Interleukin, Recombinant Proteins, Interleukin-10, Mice, Viral Proteins, Leukocytes, Mononuclear, Animals, Humans, Interleukin-2, Receptors, Interleukin-10, Cells, Cultured, Protein Binding
Herpesvirus 4, Human, Antibodies, Monoclonal, Receptors, Interleukin, Recombinant Proteins, Interleukin-10, Mice, Viral Proteins, Leukocytes, Mononuclear, Animals, Humans, Interleukin-2, Receptors, Interleukin-10, Cells, Cultured, Protein Binding
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