High affinity type I interleukin 1 receptor antagonists discovered by screening recombinant peptide libraries

Abstract

Two families of peptides that specifically bind the extracellular domain of the human type I interleukin 1 (IL-1) receptor were identified from recombinant peptide display libraries. Peptides from one of these families blocked binding of IL-1α to the type I IL-1 receptor with IC50 values of 45-140 μM. Affinity-selective screening of variants of these peptides produced ligands of much higher affinity (IC50 ≃ 2 nM). These peptides block IL-1-driven responses in human and monkey cells; they do not bind the human type I IL-1 receptor or the murine type I IL-1 receptor. This is the first example (that we know of) of a high affinity peptide that binds to a cytokine receptor and acts as a cytokine antagonist.