Screening Method for the Identification of Agents Capable of Activating CD4+CD25+ Regulatory T-Cells Through Interactions with the HIV-1 GP120 Binding Site on CD4

Abstract

The present invention relates specific activation of a regulatory T cell via a specific CD4 epitope and uses thereof, e.g. for the treatment of an autoimmune disease or an allergy or asthma or graft rejection or tolerance induction.

What is claimed is: 
     
         1 . A CD4 + CD25 +  Treg cell activator which activates CD4 + CD25 +  Treg cell via interaction with the CD4 + CD25 +  Treg cell epitope as set forth in SEQ ID NO:1, said CD4 + CD25 +  Treg cell activator being a peptide, a polypeptide, or an antibody or a binding fragment thereof with the proviso that the antibody or antibody fragment is not OKT4A, OKT4D, OKTcdr4a, MAX.12H5 and not Leu3. 
     
     
         2 . The CD4 + CD25 +  Treg cell activator according to  claim 1  wherein said CD4 + CD25 +  Treg cell activator is a peptide comprising the amino acid sequence as set forth in SEQ ID NO.: 3, SEQ ID NO.: 4, SEQ ID NO.: 5, SEQ ID NO.: 6, SEQ ID NO.: 7, SEQ ID NO.: 8, SEQ ID NO.: 9, or SEQ ID NO.: 10. 
     
     
         3 . A method of treating an individual in need thereof comprising administering a CD4 + CD25 +  Treg cell activator which activates CD4 + CD25 +  Treg cell via interaction with the CD4 + CD25 +  Treg cell epitope as set forth in SEQ ID NO:1, wherein said CD4 + CD25 +  Treg cell activator is a peptide, a polypeptide, or an antibody or a binding fragment thereof with the proviso that the antibody or antibody fragment is not OKT4A, OKT4D, OKTcdr4a, MAX.12H5 and not Leu3. 
     
     
         4 . The method of treating an individual in need thereof according to  claim 3  wherein said Treg cell activator is a peptide comprising the amino acid sequence as set forth in SEQ ID NO.: 3, SEQ ID NO.: 4, SEQ ID NO.: 5, SEQ ID NO.: 6, SEQ ID NO.: 7, SEQ ID NO.: 8, SEQ ID NO.: 9, or SEQ ID NO.: 10. 
     
     
         5 . The method of treating an individual in need thereof according to  claim 3  wherein said CD4 + CD25 +  Treg cell activator is HIV-1 gp120. 
     
     
         6 . The method of treating an individual in need thereof according to  claim 3  wherein said CD4 + CD25 +  Treg cell activator is selected from a group consisting of: NSC 13778, peptide2 which presents three HIV-1 gp120 fragments bound together through comformationally flexible scaffolds, monoclonal antibody OKT4A, monoclonal antibody OKT4D, monoclonal antibody OKTcdr4a, monoclonal antibody MAX. 12H5, and monoclonal antibody Leu3. 
     
     
         7 . Use of a CD4 + CD25 +  Treg cell activator which activates CD4 + CD25 +  Treg cell via interaction with the CD4 + CD25 +  Treg cell epitope as set forth in SEQ ID NO:1 for the preparation of a medicament for the treatment of a disease selected from a group consisting of a non-autoimmune inflammatory disease, an autoimmune inflammatory disease, an inflammatory disease due to organ transplantation; a bone marrow transplantation, and a disease due to exogenously administered self or exogenously administered non-autologous recombinant polypeptide, wherein said CD4 + CD25 +  Treg cell activator is an antibody or an antibody fragment capable of binding to the peptide as set forth in SEQ ID NO.:1 or a peptide comprising the amino acid sequence as set forth in SEQ ID NO.: 3, SEQ ID NO.: 4, SEQ ID NO.: 5, SEQ ID NO.: 6, SEQ ID NO.: 7, SEQ ID NO.: 8, SEQ ID NO.: 9, or SEQ ID NO.: 10. 
     
     
         8 . The use according to according to  claim 7  wherein said non-autoimmune inflammatory disease is selected from a group consisting of: asthma, allergic asthma, respiratory allergy, allergic rhinoconjunctivitis, allergic alveolitis, contact allergy, atopic dermatitis, neurodermatitis, food allergy, graft-versus-host disease, non-autoimmune inflammatory bowel disease, acute respiratory distress syndrome, acute inflammatory pancreatitis, burns, wound healing, skin scarring disorders, sarcoidosis, Behcet's disease, Sweet's syndrome. 
     
     
         9 . The use according to according to  claim 7  wherein said an autoimmune inflammatory disease is selected from a group consisting of: rheumatoid arthritis, rheumatic fever, systemic lupus erythematosus, ulcerative colitis, Crohn's disease, autoimmune inflammatory bowel disease, diabetes type I, gastritis, autoimmune atrophic gastritis, autoimmune hepatitis, Hashimoto's thyroiditis, thyreoiditis, multiple sclerosis, myasthenia gravis, autoimmune haemolytic anemia, Addison's disease, scleroderma, Goodpasture's syndrome, Guillain-Barre syndrome, Graves' disease, glomerulonephritis, psoriasis, pemphigus vulgaris, pemphigoid, vitiligo, idiopathic leukopenia, Sjogren's syndrome, Wegener's granulomatosis. 
     
     
         10 . The use according to according to  claim 7  wherein said CD4 + CD25 +  Treg cell activator is HIV-1 gp120. 
     
     
         11 . The use according to according to  claim 7  wherein said CD4 + CD25 +  Treg cell activator is selected from a group consisting of: NSC 13778, peptide2 which presents three HIV-1 gp120 fragments bound together through comformationally flexible scaffolds, monoclonal antibody OKT4A, monoclonal antibody OKT4D, monoclonal antibody OKTcdr4a, monoclonal antibody MAX. 12H5, and monoclonal antibody Leu3. 
     
     
         12 . A pharmaceutical composition comprising at least one CD4 + CD25 +  Treg cell activator which activates CD4 + CD25 +  Treg cell via interaction with the CD4 + CD25 +  Treg cell epitope as set forth in SEQ ID NO:1 wherein said CD4 + CD25 +  Treg cell activator is a peptide, a polypeptide, or an antibody or a binding fragment thereof with the proviso that the antibody or antibody fragment is not OKT4A, OKT4D, OKTcdr4a, MAX.12H5 and not Leu3. 
     
     
         13 . The pharmaceutical composition according to  claim 12  wherein said CD4 + CD25 +  Treg cell activator is a peptide comprising the amino acid sequence as set forth in SEQ ID NO.: 3, SEQ ID NO.: 4, SEQ ID NO.: 5, SEQ ID NO.: 6, SEQ ID NO.: 7, SEQ ID NO.: 8, SEQ ID NO.: 9, or SEQ ID NO.: 10. 
     
     
         14 . A method for reducing or preventing an unwanted immune reaction due to a exogenously administered self or exogenously administered non-autologous recombinant polypeptide comprising administering to a being in need thereof a suitable amount of a pharmaceutical composition comprising a CD4 + CD25 +  Treg cell activator which is an antibody or an antibody fragment capable of binding to the peptide as set forth in SEQ ID NO.:1 or is a peptide comprising the amino acid sequence as set forth in SEQ ID NO.: 3, SEQ ID NO.: 4, SEQ ID NO.: 5, SEQ ID NO.: 6, SEQ ID NO.: 7, SEQ ID NO.: 8, SEQ ID NO.: 9, or SEQ ID NO.: 10. 
     
     
         15 . The method according to  claim 14  wherein said CD4 + CD25 +  Treg cell activator is HIV-1 gp120. 
     
     
         16 . The method according to  claim 14  wherein said Treg cell activator is selected from a group consisting of: NSC 13778, peptide 2 which presents three HIV-1 gp120 fragments bound together through comformationally flexible scaffolds, monoclonal antibody OKT4A, monoclonal antibody OKT4D, monoclonal antibody OKTcdr4a, monoclonal antibody MAX. 12H5, and monoclonal antibody Leu3.