Interleukin-18 mutants
The invention provides mutants of IL-18 with lower affinity to IL-18BP than the wild type IL-18 molecule.
1. An isolated and purified IL-18 mutant polypeptide, comprising a mutation in an amino acid residue Lys-89 of the wildtype IL-18 polypeptide encoded by SEQ ID NO: 1, wherein the mutation is a non-conservative substitution and wherein the mutant polypeptide binds to an IL-18 receptor and wherein binding of the mutant polypeptide to IL-18 binding protein is reduced.
2. An isolated and purified IL-18 mutant polypeptide, comprising a mutation in a Glu-42 residue and a Lys-89 residue of the wildtype IL-18 polypeptide encoded by SEQ ID NO: 1.
3. An isolated and purified IL-18 mutant polypeptide, comprising a mutation in two or more amino acid residues selected from a group consisting of Glu-42, and Lys-89 of the wildtype IL-18 polypeptide encoded by SEQ ID NO: 1, wherein both the Glu-42 residue and the Lys-89 residues are each replaced with a non-polar amino acid.
4. The polypeptide according to claim 3 , where both the Glu-42 and the Lys-89 residues are each replaced with an Ala residue.
5. A pharmaceutical composition comprising a polypeptide according to claims 1 , 2 , 3 or 4 , and a pharmaceutically acceptable carrier.