Method of inducing SHC phosphorylation of inducing the SHC/MAPK pathway by administering a peptide of IL-2
The present invention relates to new peptides of IL-2, derivatives thereof, and their use as therapeutic agents.
1. A method of inducing in a patient, SHC phosphorylation or inducing the SHC/MAPK pathway in T lymphocytes, wherein said method comprises:
administering to said patient a peptide consisting of SEQ ID NO: 4 or a peptide consisting of SEQ ID NO: 4 containing one conservative mutation, wherein said peptide binds to the IL-2β chain or the monoclonal antibodies produced by H2-8 hybridoma, sufficient to induce SHC phosphorylation or induce the SHC/MAPK pathway in T lymphocytes.
2. The method of claim 1 , wherein said peptide consists of SEQ ID NO: 4.
3. The method of claim 1 , wherein said peptide is the peptide consisting of SEQ ID NO: 4 containing one conservative mutation.
4. The method of claim 3 , wherein said conservative mutation is a replacement of a non-polar R-group by another non-polar R-group.
5. The method of claim 3 , wherein said conservative mutation is a replacement of an uncharged non-polar R-group by another uncharged non-polar R-group.
6. The method of claim 3 , wherein said conservative mutation is a replacement of a charged polar R-group by another charged polar R-group.
7. The method of claim 3 , wherein Lys is substituted for Arg, or vice versa so that a positive charge is maintained.
8. The method of claim 3 , wherein Glu is substituted for Asp, or vice versa so that a negative charge is maintained.
9. The method of claim 3 , wherein Asp is substituted for Glu.
10. The method of claim 3 , wherein one or more Ser is substituted for Thr.
11. The method of claim 3 , wherein one or more Gln is substituted for Asn.
12. The method of claim 1 , wherein said method is a method of inducing SHC phosphorylation.
13. The method of claim 1 , wherein said method is a method of inducing the SHC/MAPK pathway.
14. The method of claim 1 , wherein said patient suffers from a disease selected from the group consisting of metastatic melanoma, renal adenocarcinoma, melanoma, colorectal cancer, lung adenocarcinoma, breast cancer, ovarian cancer, viral infections, HIV infection and autoimmune disorders.
15. The method of claim 1 further comprising administering to said patient an effective amount of a peptide consisting of SEQ ID NO: 4 or a peptide consisting of SEQ ID NO: 4 containing one conservative mutation, in admixture with a cytokine.
16. The method of claim 15 , wherein the cytokine is IL-2, IL-4, IL-9 or IL-15.
17. The method of claim 15 , wherein 1×10 6 international units of IL-2 is administered in admixture with the effective amount of a peptide consisting of SEQ ID NO: 4 or a peptide consisting of SEQ ID NO: 4 containing one conservative mutation.