Use of soluble forms of CD83 and nucleic acids encoding them for the treatment or prevention of diseases
The present invention provides for the use of soluble forms of CD83 and nucleic acids encoding them for the treatment of diseases caused by the dysfunction or undesired function of a cellular immune response involving dendritic cells, T cells and/or B cells. The invention moreover provides soluble CD83 molecules specifically suited for said purpose, antibodies against said specific soluble CD83 proteins and assay methods and kits comprising said antibodies.
1. A nucleic acid encoding a monomeric soluble CD83 protein selected from the group consisting of:
i) a soluble CD83 protein consisting of amino acid residues 20 to 144 of SEQ ID NO: 2;
ii) a soluble CD83 protein consisting of amino acid residues 20 to 145 of SEQ ID NO:2,
iii) a soluble CD83 protein consisting of amino acid residues 1 to 129 of SEQ ID NO: 8; and
iv) a soluble CD83 protein consisting of amino acid residues 1 to 130 of SEQ ID NO:8;
wherein in each of i) through iv) the third or fifth cysteine residue is substituted with an amino acid residue selected from the group consisting of serine, alanine, glycine, valine, threonine, aspartic acid, glutamic acid, arginine, lysine, histidine, asparagine, glutamine and tyrosine; wherein said third cysteine residue corresponds to residue 100 of SEQ ID NO: 2 or residue 85 of SEQ ID NO: 8, and wherein said fifth cysteine residue corresponds to residue 129 of SEQ ID NO: 2 or residue 114 of SEQ ID NO: 8.
2. The nucleic acid encoding a monomeric soluble CD83 protein of claim 1 , wherein said cysteine residue of said monomeric soluble CD83 protein is substituted with serine.
3. The nucleic acid encoding a monomeric soluble CD83 protein of claim 1 , wherein said monomeric soluble CD83 protein consists of amino acid residue 20 to 145 of SEQ ID NO:2 and wherein the third or fifth cysteine residue is substituted with an amino acid residue selected from the group consisting of serine, alanine, glycine, valine, threonine, aspartic acid, glutamic acid, arginine, lysine, histidine, asparagine, glutamine and tyrosine.
4. The nucleic acid encoding a monomeric soluble CD83 protein of claim 3 , wherein the third cysteine residue of said monomeric soluble CD83 protein has been substituted with a serine residue.
5. The nucleic acid encoding a monomeric soluble CD83 protein of claim 1 , wherein said monomeric soluble CD83 protein consists of amino acid residues 1 to 130 of SEQ ID NO:8, and wherein the third or fifth cysteine residue is substituted with an amino acid residue selected from the group consisting of serine, alanine, glycine, valine, threonine, aspartic acid, glutamic acid, arginine, lysine, histidine, asparagine, glutamine and tyrosine.
6. The nucleic acid encoding a monomeric soluble CD83 protein of claim 5 , wherein the third cysteine residue, corresponding to amino acid residue 85, is substituted with an amino acid residue which is serine.
7. The nucleic acid encoding a monomeric soluble CD83 protein of claim 1 , wherein the third cysteine residue of said monomeric soluble CD83 protein, corresponding to residue 100 of SEQ ID NO:2 or residue 85 of SEQ ID NO:8, is substituted.
8. The nucleic acid encoding a monomeric soluble CD83 protein of claim 7 , wherein the third cysteine residue of said monomeric soluble CD83 protein is substituted with a serine residue.
9. The nucleic acid encoding a monomeric soluble CD83 protein of claim 1 , wherein the fifth cysteine residue of said monomeric soluble CD83 protein, corresponding to residue 129 of SEQ ID NO:2 or residue 144 of SEQ ID NO:8, is substituted.
10. The nucleic acid encoding a monomeric soluble CD83 protein of claim 9 , wherein the fifth cysteine residue of said monomeric soluble CD83 protein is substituted with a serine residue.
11. The nucleic acid encoding a monomeric soluble CD83 protein of claim 1 , which consists of amino acid residues 1 to 130 of SEQ ID NO:10.
12. A nucleic acid comprising a start codon operatively linked to a sequence encoding a monomeric soluble CD83 protein of the CD83 family of proteins selected from the group consisting of:
i) a soluble CD83 protein consisting of amino acid residues 20 to 144 of SEQ ID NO: 2; and
ii) a soluble CD83 protein consisting of amino acid residues 20 to 145 of SEQ ID NO: 2;
wherein in each of i) and ii) the third or fifth cysteine residue is substituted with an amino acid residue selected from the group consisting of serine, alanine, glycine, valine, threonine, aspartic acid, glutamic acid, arginine, lysine, histidine, asparagine, glutamine and tyrosine; wherein said third cysteine residue corresponds to residue 100 of SEQ ID NO: 2, and wherein said fifth cysteine residue corresponds to residue 129 of SEQ ID NO: 2.
13. The nucleic acid of claim 12 , wherein said sequence consists of amino acid residues 20 to 144 of SEQ ID NO:2, and wherein the third cysteine residue of said encoded monomeric soluble CD83 protein, corresponding to residue 100 of SEQ ID NO:2, is substituted with a serine residue.
14. The nucleic acid of claim 12 , wherein said sequence consists of amino acid residues 20 to 145 of SEQ ID NO:2, and wherein the fifth cysteine residue of said encoded monomeric soluble CD83 protein, corresponding to residue 129 of SEQ ID NO:2, is substituted with a serine residue.
15. An isolated host cell comprising the nucleic acid of claim 12 .
16. The host cell of claim 15 , wherein said cell is Escherichia coli.
17. A method for producing a soluble CD83 protein comprising culturing the host cell of claim 15 such that the protein is expressed by the host cell.
18. The method of claim 17 , wherein said host cell is a prokaryotic host cell which is Escherichia coli.
19. The nucleic acid of claim 12 , wherein said sequence consists of amino acid residues 20 to 145 of SEQ ID NO:2, and wherein the third cysteine residue of said encoded monomeric soluble CD83 protein, corresponding to residue 100 of SEQ ID NO:2, is substituted with a serine residue.