Alteration of immune response using pan DR-binding peptides
The present invention provides compositions and methods of inhibiting or inducing activation of T cells in a patient. The methods comprise administering a therapeutically effective dose of pharmaceutical compositions comprising a pharmaceutically acceptable carrier and peptides of between about 4 and about 20 residues, that bind antigen binding sites on MHC molecules encoded by substantially all alleles of a DR locus. These peptides are referred to as pan DR binding peptides. The pan DR binding peptides can be used to inhibit immune responses associated with immunopathologies, such as autoimmunity, allograft rejection and allergic responses. The peptides can also be used in combination with CTL peptides to enhance a CTL response.
1. A polynucleotide encoding a fusion protein, the fusion protein comprising
at least one pan DR binding peptide comprising AKFVAAWTLKAAA (SEQ ID NO:22) and at least one CTL-inducing peptide.
2. An expression vector comprising the polynucleotide of claim 1 .
3. The polynucleotide of claim 1 , wherein the fusion protein comprises multiple pan DR peptides.
4. The polynucleotide of claim 1 , wherein the fusion protein comprises a homopolymer of pan DR peptides.
5. The polynucleotide of claim 1 , wherein the fusion protein comprises a heteropolymer of pan DR peptides.
6. The polynucleotide of claim 1 , wherein the fusion protein further comprises a heteropolymer with repeating units.
7. The polynucleotide of claim 1 , wherein the fusion protein further comprises an antibody-inducing peptide.
8. A polynucleotide encoding a fusion protein, the fusion protein comprising at least one pan DR binding peptide comprising AKFVAAWTLKAAA (SEQ ID NO:22) and at least one T helper peptide.
9. An expression vector comprising the polynucleotide of claim 8 .
10. The polynucleotide of claim 8 , wherein the fusion protein comprises multiple pan DR peptides.
11. The polynucleotide of claim 8 , wherein the fusion protein comprises a homopolymer of pan DR peptides.
12. The polynucleotide of claim 8 , wherein the fusion protein comprises a heteropolymer of pan DR peptides.
13. The polynucleotide of claim 8 , wherein the fusion protein further comprises a heteropolymer with repeating units.
14. The polynucleotide of claim 8 , wherein the fusion protein further comprises an antibody-inducing peptide.