HIGH-AFFINITY TYPE-I INTERLEUKIN-1 RECEPTOR ANTAGONISTS DISCOVERED BYSCREENING RECOMBINANT PEPTIDE LIBRARIES

Two families of peptides that specifically bind the extracellular doma in of the human type I interleukin 1 (IL-1) receptor were identified f rom recombinant peptide display libraries. Peptides from one of these families blocked binding of IL-1 alpha to the type I IL-1 receptor wit h IC50 values of 45-140 mu M. Affinity-selective screening of variants of these peptides produced ligands of much higher affinity (IC50 appr oximate to 2 nM). These peptides block IL-1-driven responses in human and monkey cells; they do not bind the human type II IL-1 receptor or the murine type I IL-1 receptor. This is the first example (that we kn ow of) of a high affinity peptide that binds to a cytokine receptor an d acts as a cytokine antagonist.