Modulation of immune response and methods based thereon

Abstract

The present invention relates to methods for the prevention and/or treatment of cardiovascular and allergic diseases and disorders, methods for inhibiting the growth of, or reducing the volume of, a solid tumor, as well as methods for preventing progression to AIDS in an HIV-infected human, by administering a peptide derived from T cell receptors, or a derivative thereof The present invention also relates to peptides derived from T-cell receptors, and derivatives thereof, which are useful in such methods. The peptides are selected from the group consisting of Cys Lys Pro Ile Ser Gly His Asn Ser Leu Phe Trp Tyr Arg Gln Thr (SEQ ID NO:1), Ala Asn Tyr Gly Tyr Thr Phe Gly Ser Gly Thr Arg Leu Thr Val Val (SEQ ID NO:2), Leu Lys Ile Gln Pro Ser Glu Pro Arg Asp Ser Ala Val Tyr Leu Cys Ala (SEQ ID NO:3), Leu Thr Ile Gln Arg Thr Gln Gln Glu Asp Ser Ala Val Tyr Leu Cys Ala (SEQ ID NO:4), Leu Ile Leu Glu Ser Ala Ser Thr Asn Gln Thr Ser Met Tyr Leu Cys Ala (SEQ ID NO:5), Leu Thr Val Ser Gly Leu Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser (SEQ ID NO:6), Leu Ala Ile Ser Gly Leu Glu Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Ala (SEQ ID NO:7), Phe Thr Ile Ser Gly Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln (SEQ ID NO:8), Leu Thr Ile Ser Gly Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln (SEQ ID NO:9), Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Phe Cys Ser (SEQ ID NO:10) and Leu Thr Ile Asn Pro Val Glu Ala Asp Asp Val Ala Thr Tyr Tyr Cys Gln (SEQ ID NO: 11), Ala Asn Tyr Gly Tyr Thr Phe Gly Ser Gly Thr Lys Leu Thr Val Val (SEQ ID NO: 12), Ala Asn Tyr Gly Tyr Thr Phe Gly Ser Gly Thr Glu Leu Thr Val Val (SEQ ID NO:13), Ala Asn Tyr Gly Tyr Thr Phe Gly Ser Gly Thr Asp Leu Thr Val Val (SEQ ID NO:14), Thr Phe Gly Xaa Gly Thr Yaa, wherein Xaa is any amino acid and Yaa is Arg, Lys, Asp, Glu, His or other charged amino acid molecule (SEQ ID NO:15), or a derivative thereof.

1 - 25 . (canceled)  
     
     
         26 . A method of increasing production of at least one Th1 cytokine or decreasing production of at least one Th2 cytokine, comprising administering to a non-human animal an effective amount of a peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and Thr Phe Gly Xaa Gly Thr Yaa, wherein Xaa is any amino acid and Yaa is Arg, Lys, Asp, Glu, His or SEQ ID NO: 15, or a derivative thereof.  
     
     
         27 . The method of  claim 26 , wherein the non-human animal is a cow sheep, pig or chicken.  
     
     
         28 . The method of  claim 26 , wherein the non-human animal is free of infection with an immunodeficiency-type retrovirus.  
     
     
         29 . The method of  claim 26 , wherein the immunodeficiency-type retrovirus is feline immunodeficiency virus.  
     
     
         30 . A method of reversing the deleterious effects of infection with an immunodeficiency-type retrovirus comprising administering to a non-human animal an effective amount of a peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and Thr Phe Gly Xaa Gly Thr Yaa, wherein Xaa is any amino acid and Yaa is Arg, Lys, Asp, Glu, His or SEQ ID NO: 15, or a derivative thereof.  
     
     
         31 . The method of  claim 30 , wherein the non-human animal is a cow sheep, pig or chicken.  
     
     
         32 . A method for the treatment of a disease or disorder of the cardiovascular system, comprising administering to a non-human animal an effective amount of a peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and Thr Phe Gly Xaa Gly Thr Yaa, wherein Xaa is any amino acid and Yaa is Arg, Lys, Asp, Glu, His or SEQ ID NO: 15, or a derivative thereof.  
     
     
         33 . The method of  claim 32 , wherein the non-human animal is a cow sheep, pig or chicken.  
     
     
         34 . The method of  claim 32 , wherein the disease or disorder of the cardiovascular system is selected from the group consisting of atherosclerosis, arteriosclerosis, atherosclerotic heart disease, reperfusion injury, cardiac arrest, myocardial infarction, thrombus formation and retrovirus-induced cardiovascular dysfunction.  
     
     
         35 . A method for the treatment of an allergic disease or disorder characterized by increased IgE production, comprising administering to a non-human animal an effective amount of a peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and Thr Phe Gly Xaa Gly Thr Yaa, wherein Xaa is any amino acid and Yaa is Arg, Lys, Asp, Glu, His or SEQ ID NO: 15, or a derivative thereof.  
     
     
         36 . The method of  claim 35 , wherein the allergic disease or disorder is selected from the group consisting of allergy, asthma, delayed hypersensitivity, septic shock and anaphylactic shock.  
     
     
         37 . The method of  claim 35 , wherein the non-human animal is a cow sheep, pig or chicken.  
     
     
         38 . A method for inhibiting the growth of a solid tumor or reducing the volume of a solid tumor, comprising administering to a non-human animal an effective amount of a peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and Thr Phe Gly Xaa Gly Thr Yaa, wherein Xaa is any amino acid and Yaa is Arg, Lys, Asp, Glu, His or SEQ ID NO: 15, or a derivative thereof.  
     
     
         39 . The method of  claim 38 , wherein the solid tumor is selected from the group consisting of sarcomas, carcinomas and lymphomas.  
     
     
         40 . The method of  claim 38 , wherein the non-human animal is a cow sheep, pig or chicken.  
     
     
         41 . The method of  claim 38 , wherein the solid tumor is a tumor of the germ line or is a tumor of the central nervous system, or is a breast cancer tumor, prostate cancer tumor, cervical cancer tumor, uterine cancer tumor, lung cancer tumor, ovarian cancer tumor, testicular cancer tumor, thyroid cancer tumor, astrocytoma, glioma, pancreatic cancer tumor, stomach cancer tumor, liver cancer tumor, colon cancer tumor, or a melanoma tumor.  
     
     
         42 . The method of  claim 41 , wherein the non-human animal is a cow sheep, pig or chicken.  
     
     
         43 . A method for preventing immunosuppression or suppressing progression to immune dysfunction or cytokine dysregulation in a non-human animal infected with a viral, fungal, or bacterial infectious agent other than an immunodeficiency-type retrovirus, comprising administering to the non-human animal an effective amount of a peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and Thr Phe Gly Xaa Gly Thr Yaa, wherein Xaa is any amino acid and Yaa is Arg, Lys, Asp, Glu, His or SEQ ID NO: 15, or a derivative thereof.  
     
     
         44 . The method of  claim 43 , wherein the non-human animal is a cow sheep, pig or chicken.