The EBV IL-10 homologue is a selective agonist with impaired binding to the IL-10 receptor.
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 alpha.
Liu
Y
Y
Department of Molecular Biology, DNAX Research Institute, Palo Alto, CA 94304, USA.
de Waal Malefyt
R
R
Briere
F
F
Parham
C
C
Bridon
J M
JM
Banchereau
J
J
Moore
K W
KW
Xu
J
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002478:Cells, Cultured; D004854:Herpesvirus 4, Human / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10; D007376:Interleukin-2 / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D051379:Mice; D011485:Protein Binding / Q000276:immunology; D018123:Receptors, Interleukin / Q000819:agonists* / Q000187:drug effects* / Q000378:metabolism*; D053701:Receptors, Interleukin-10; D011994:Recombinant Proteins / Q000494:pharmacology; D014764:Viral Proteins / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; C066460:BCRF1 protein, Human herpesvirus 4; D007376:Interleukin-2; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D011994:Recombinant Proteins; D014764:Viral Proteins; D016753:Interleukin-10