Human cytokine as ligand of the z-alpha receptor and uses thereof

摘要

The invention provides a fusion protein comprising at least four polypeptides, wherein the order of polypeptides from N-terminus to C-terminus are: a first polypeptide that comprises a sequence of amino acid residues from 41 to 56 of SEQ ID NO:2; a first spacer of 6-27 amino acid residues; a second polypeptide that comprises a sequence of amino acid residues selected from the group consisting of: (a) IL-2 helix B residues 53-75 of SEQ ID NO:111; (b) IL-4 helix B residues 65-83 of SEQ ID NO:112; (c) IL-15 helix B residues 84-101 of SEQ ID NO:113; (d) GMCSF helix B residues 72-81 of SEQ ID NO:114; and (e) amino acid residues 69-84 of SEQ ID NO:2; a second spacer of 5-11 amino acid residues; a third polypeptide that comprises a sequence of amino acid residues selected from the group consisting of: (a) IL-2 helix C residues 87-99 of SEQ ID NO:111; (b) IL-4 helix C residues 95-118 of SEQ ID NO:112; (c) IL-15 helix C residues 107-119 of SEQ ID NO:113; (d) GMCSF helix C residues 91-102 of SEQ ID NO:2; (e) amino acid residues 92-105 of SEQ ID NO:2; a third spacer of 3-29 amino acid residues; and a fourth polypeptide that comprises a sequence of amino acid residues selected from the group consisting of: (a) IL-2 helix D residues 103-121 of SEQ ID NO:111; (b) IL-15 helix D residues 134-157 of SEQ ID NO:112; (c) IL-4 helix D residues 134-160 of SEQ ID NO:113; (d) GMCSF helix D residues 120-131 of SEQ ID NO:114; and (e) amino acid residues 135-148 of SEQ ID NO:2.