Use of HLA-A*11:01-restricted hepatitis B virus (HBV) peptides for identifying HBV-specific CD8+ T cells
View Patent ↗The present invention relates to peptides and their ability to identify and bind to T cells specific for HBV-infected hepatocytes. In a first aspect of the invention, there is provided a peptide comprising an amino acid sequence selected from the group consisting of STLPETAVVRR (SEQ ID NO: 21), STLPETAVVR (SEQ ID NO: 22), STLPETTVVRR (SEQ ID NO: 23), STLPETTVTRR (SEQ ID NO: 24), STPPETTVVRR (SEQ ID NO: 25), STLPETTVVGR (SEQ ID NO: 26) and STIPETTVVRR (SEQ ID NO: 27), wherein the peptide is derived from Hepatitis B virus core169 and is capable of binding HLA-A*1101 and when bound to HLA-A*1101 is capable of identifying T cells specific for Hepatitis B virus. In a second aspect of the invention, there is provided a T cell expressing a T cell receptor (TCR) molecule, wherein the TCR molecule comprises an amino acid sequence selected from the group consisting of CASGDSNSPLHF (SEQ ID NO: 17), CASSGGQIVYEQYF (SEQ ID NO: 18), CSARGGRGGDYTF (SEQ ID NO: 19) and CASSQDWTEAFF (SEQ ID NO: 20), and wherein the TCR molecule is able to bind to a peptide according to the first aspect of the invention.
1. A method for identifying Hepatitis B virus antigen-specific T cells, the method comprising contacting a population of T cells with a peptide comprising an amino acid sequence selected from the group consisting of STLPETAVVRR (SEQ ID NO: 21), STLPETAVVR (SEQ ID NO: 22), STLPETTVTRR (SEQ ID NO: 24), STPPETTVVRR (SEQ ID NO: 25), STLPETTVVGR (SEQ ID NO: 26) and STIPETTVVRR (SEQ ID NO: 27), wherein the peptide is less than 30 amino acids long and is capable of binding HLA-A* 1101 and when bound to HLA-A* 1101 is capable of identifying T cells specific for Hepatitis B virus.
2. A T cell receptor (TCR) molecule comprising a TCR beta chain complementarity determining region 3 (CDR3) comprising an amino acid sequence selected from the group consisting of: CASGDSNSPLHF (SEQ ID NO: 17), CASSGGQIVYEQYF (SEQ ID NO: 18), CSARGGRGGDYTF (SEQ ID NO: 19) and CASSQDWTEAFF (SEQ ID NO: 20), wherein the TCR molecule is able to bind to a peptide, wherein the peptide comprises an amino acid sequence selected from the group consisting of STLPETAVVRR (SEQ ID NO: 21), STLPETAVVR (SEQ ID NO: 22), STLPETTVIRR (SEQ ID NO: 24), STPPETTVVRR (SEQ ID NO: 25), STLPETTVVGR (SEQ ID NO: 26) and STIPETTVVRR (SEQ ID NO: 27).
3. A polynucleotide encoding the TCR molecule according to claim 2 .
4. The polynucleotide according to claim 3 , comprising a sequence selected from the group consisting of SEQ ID NOs: 1 to 16.
5. An expression vector comprising the polynucleotide according to claim 3 .
6. An isolated host cell comprising the polynucleotide according to claim 3 .
7. The isolated host cell according to claim 6 , wherein the host cell is a T cell derived from a patient.
8. An isolated T cell modified to express the TCR molecule according to claim 2 .
9. A pharmaceutical composition comprising a peptide and a pharmaceutically acceptable carrier, wherein the peptide comprises an amino acid sequence selected from the group consisting of STLPETAVVRR (SEQ ID NO: 21), STLPETAVVR (SEQ ID NO: 22), STLPETTVTRR (SEQ ID NO: 24), STPPETTVVRR (SEQ ID NO: 25), STLPETTVVGR (SEQ ID NO: 26) and STIPETTVVRR (SEQ ID NO: 27), wherein the peptide is less than 30 amino acids long and is capable of binding HLA-A*1101.
10. A method of treating a Hepatitis B virus infection in an individual, the method comprising administering to the individual an effective amount of a peptide, wherein the peptide comprises an amino acid sequence selected from the group consisting of STLPETAVVRR (SEQ ID NO: 21), STLPETAVVR (SEQ ID NO: 22), STLPETTVIRR (SEQ ID NO: 24), STPPETTVVRR (SEQ ID NO: 25), STLPETTVVGR (SEQ ID NO: 26) and STIPETTVVRR (SEQ ID NO: 27), wherein the peptide is less than 30 amino acids long and is capable of binding HLA-A*1101.
11. A method of combating a Hepatitis B virus infection in a patient which carries HLA-A*1101, the method comprising:
(a) obtaining T cells from the patient;
(b) introducing into the T cells a polynucleotide encoding the TCR molecule according to claim 2 ; and
(c) introducing the T cells produced in step (b) into the patient.
12. The method according to claim 11 , wherein the polynucleotide is transfected into or introduced to the T cells by electroporation.
13. An isolated host cell comprising the expression vector according to claim 5 .
14. A pharmaceutical composition comprising the isolated host cell according to claim 7 and a pharmaceutically acceptable carrier.
15. A vaccine against Hepatitis B virus infection comprising the isolated T cell according to claim 8 .
16. A method of treating a Hepatitis B virus infection in an individual, the method comprising administering to the individual an effective amount of the isolated T cell according to claim 8 .