Temporal associations between interleukin 22 and the extracellular domains of IL-22R and IL-10R2.
Interleukin 22 (IL-22) is a cytokine induced during both innate and adaptive immune responses. It can effect an acute phase response, implicating a role for IL-22 in mechanisms of inflammation. IL-22 requires the presence of the IL-22 receptor (IL-22R) and IL-10 receptor 2 (IL-10R2) chains, two members of the class II cytokine receptor family (CRF2), to effect signal transduction within a cell. We studied the interaction between human IL-22 and the extracellular domains (ECD) of its receptor chains in an enzyme-linked immunoabsorbant assay (ELISA)-based format, using biotinylated IL-22 (bio-IL-22) and receptor-fusions containing the ECD of a receptor fused to the Fc of hIgG1 (IL-22R-Fc and IL-10R2-Fc). IL-22 has measurable affinity for IL-22R-Fc homodimer and undetectable affinity for IL-10R2. IL-22 has substantially greater affinity for IL-22R/IL-10R2-Fc heterodimers. Further analyses involving sequential additions of receptor homodimers and cytokine indicates that the IL-10R2(ECD) binds to a surface created by the interaction between IL-22 and the IL-22R(ECD), and thereby further stabilizes the association of IL-22 within this cytokine-receptor-Fc complex. Both a neutralizing rat monoclonal antibody, specific for human IL-22, and human IL-22BP-Fc, an Fc-fusion of the secreted IL-22 binding-protein and proposed natural antagonist for IL-22, bind to similar cytokine epitopes that may overlap the binding site for IL-22R(ECD). Another rat monoclonal antibody, specific for IL-22, binds to an epitope that may overlap a separate binding site for IL-10R2(ECD). We propose, based on this data, a temporal model for the development of a functional IL-22 cytokine-receptor complex.
Li
Jing
J
Wyeth Research, 87 Cambridge Park Drive, Cambridge, MA 02140, USA.
Tomkinson
Kathy N
KN
Tan
Xiang-Yang
XY
Wu
Paul
P
Yan
Grace
G
Spaulding
Vikki
V
Deng
Bijia
B
Annis-Freeman
Bethany
B
Heveron
Kathleen
K
Zollner
Richard
R
De Zutter
Gerard
G
Wright
Jill F
JF
Crawford
Tara K
TK
Liu
Wei
W
Jacobs
Kenneth A
KA
Wolfman
Neil M
NM
Ling
Vincent
V
Pittman
Debra D
DD
Veldman
Geertruida M
GM
Fouser
Lynette A
LA
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D019281:Dimerization; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D007378:Interleukins / Q000378:metabolism* / Q000494:pharmacology; D018123:Receptors, Interleukin / Q000187:drug effects / Q000378:metabolism*; D053701:Receptors, Interleukin-10; D013997:Time Factors; D000097043:Interleukin-22
D007378:Interleukins; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D000097043:Interleukin-22; C415369:interleukin-22 receptor