T cell receptors specific for immunodominant CTL epitopes of HCV
The present invention relates generally to the field of immunology. More particularly, aspects of the invention concern the discovery of several T cell receptors (TCRs) that are specific for an immunodominant CTL epitope of hepatitis C virus (HCV). Embodiments include TCRs, DNAs encoding TCRs, methods of making TCRs, and methods of using TCRs to treat, prevent or inhibit hepatitis C virus (HCV) proliferation.
1. An isolated nucleic acid comprising a sequence encoding a peptide that comprises the sequence of SEQ ID NO:1, wherein said isolated nucleic acid is codon-optimized for expression in humans.
2. The isolated nucleic acid of claim 1 , wherein said isolated nucleic acid comprises SEQ ID NO:76.
3. The isolated nucleic acid of claim 1 , wherein said isolated nucleic acid comprises SEQ ID NO:78.
4. An isolated cell comprising the isolated nucleic acid of claim 1 .
5. The isolated cell of claim 4 , wherein said isolated nucleic acid comprises SEQ ID NO:63.
6. The isolated cell of claim 4 , wherein the peptide that comprises the sequence of SEQ ID NO: 1 comprises the sequence of SEQ ID NO:72.
7. The isolated cell of claim 4 , wherein said isolated nucleic acid comprises SEQ ID NO:74.
8. The isolated cell of claim 4 , wherein said isolated nucleic acid comprises SEQ ID NO:76.
9. The isolated cell of claim 4 , wherein said isolated nucleic acid comprises SEQ ID NO:78.
10. A host-expression vector comprising the isolated nucleic acid of claim 1 .
11. The host-expression vector of claim 10 , wherein said isolated nucleic acid comprises SEQ ID NO:63.
12. The host-expression vector of claim 10 , wherein said peptide that comprises the sequence of SEQ ID NO:1 comprises the sequence of SEQ ID NO:72.
13. The host expression vector of claim 12 , wherein said isolated nucleic acid comprises SEQ ID NO:74.
14. The host-expression vector of claim 12 , wherein said isolated nucleic acid comprises SEQ ID NO:76.
15. The host-expression vector of claim 12 , wherein said isolated nucleic acid comprises SEQ ID NO:78.
16. The isolated nucleic acid of claim 1 , wherein said nucleic acid further comprises a nucleic acid sequence encoding a peptide that comprises the sequence of SEQ ID NO:2.
17. The isolated nucleic acid of claim 16 , wherein said isolated nucleic acid comprises SEQ ID NO:64.
18. The isolated nucleic acid of claim 16 , wherein the sequence that encodes SEQ ID NO:2 encodes SEQ ID NO:73.
19. The isolated nucleic acid of claim 18 , wherein said isolated nucleic acid comprises SEQ ID NO:75.
20. The isolated nucleic acid of claim 16 , wherein said isolated nucleic acid comprises SEQ ID NO:77.
21. The isolated nucleic acid of claim 16 , wherein said isolated nucleic acid comprises SEQ ID NO:79.
22. The isolated nucleic acid of claim 16 , wherein the isolated nucleic acid that encodes SEQ ID NO: 1 and that encodes SEQ ID NO:2 further encodes a 2A protease cleavage site positioned between SEQ ID NO: 1 and SEQ ID NO:2.
23. The isolated nucleic acid of claim 1 , wherein said isolated nucleic acid comprises SEQ ID NO:63.
24. The isolated nucleic acid of claim 1 , wherein said peptide that comprises the sequence of SEQ ID NO:1 comprises the sequence of SEQ ID NO:72.
25. The isolated nucleic acid of claim 1 , wherein said isolated nucleic acid comprises SEQ ID NO:74.