Compositions and methods for treating or preventing unwanted immune responses are provided. The compositions relate to novel soluble CD83 (sCD83) polypeptides and nucleic acids encoding such polypeptides, improved (sCD83) formulations, and the use of such polypeptides and formulations in the treatment or prevention of allergy, autoimmune disease and transplant rejection. A sCD83 polypeptide is provided, comprising SEQ ID NO:7 or an amino acid sequence having at least 70% identity to SEQ ID NO:7; wherein one or more of amino acid residues 12, 20, 85 and 92 of SEQ ID NO:7 is an amino acid other than cysteine; and optionally, one or more of amino acid residues 1, 2, 3, 4 and 130 are absent.