Antigen-specific T cell receptors and T cell epitopes
The present invention relates to efficient methods for providing antigen-specific lymphoid cells. These lymphoid cells may be used to provide antigen specific T cell receptors having a defined MHC restriction and to identify immunologically relevant T cell epitopes. Furthermore, the present invention relates to antigen-specific T cell receptors and T cell epitopes and their use in immunotherapy.
1. A nucleic acid encoding a T cell receptor selected from the group consisting of:
(I) a T cell receptor comprising:
(i) a T cell receptor α-chain comprising all three CDR sequences of T cell receptor α-chain of SEQ ID NO: 46, and
(ii) a T cell receptor β-chain comprising all three of the CDR sequences of T cell receptor β-chain of SEQ ID NO: 47; and
(II) a T cell receptor comprising:
(i) a T cell receptor α-chain comprising the T cell receptor α-chain sequence of SEQ ID NO: 46, and
(ii) a T cell receptor β-chain comprising the T cell receptor β-chain sequence of SEQ ID NO: 47.
2. An antigen-specific lymphoid cell produced by transferring into a lymphoid cell (i) a nucleic acid encoding a T cell receptor α-chain comprising the T cell receptor α-chain sequence of SEQ ID NO: 46 and a nucleic acid encoding a T cell receptor β-chain comprising the T cell receptor β-chain sequence of SEQ ID NO: 47 or (ii) a nucleic acid encoding a T cell receptor comprising the T cell receptor α-chain sequence of SEQ ID NO: 46 and the T cell receptor β-chain sequence of SEQ ID NO: 47.
3. A pharmaceutical composition comprising the antigen-specific lymphoid cell of claim 2 .
4. An antigen-specific lymphoid cell produced by transferring into a lymphoid cell (i) a nucleic acid encoding a T cell receptor α-chain comprising all three of the CDR sequences of the T cell receptor α-chain sequence of SEQ ID NO: 46 and a nucleic acid encoding a T cell receptor β-chain comprising all three of the CDR sequences of the T cell receptor β-chain sequence of SEQ ID NO: 47 or (ii) a nucleic acid encoding a T cell receptor comprising all three of the CDR sequences of the T cell receptor α-chain sequence of SEQ ID NO: 46 and all three of the CDR sequences the T cell receptor β-chain sequence of SEQ ID NO: 47.
5. A pharmaceutical composition comprising the antigen-specific lymphoid cell of claim 4 .
6. The antigen-specific lymphoid cell of claim 2 , wherein the nucleic acid is RNA.
7. The antigen-specific lymphoid cell of claim 6 , wherein the RNA is in vitro transcribed RNA (IVT RNA).
8. The antigen-specific lymphoid cell of claim 2 , wherein the lymphoid cell is selected from the group consisting of a lymphocyte, lymphoblast and plasma cell.
9. The antigen-specific lymphoid cell of claim 2 , wherein the lymphoid cell is a T cell lacking endogenous expression of a T cell receptor.
10. The antigen-specific lymphoid cell of claim 4 , wherein the nucleic acid is RNA.
11. The antigen-specific lymphoid cell of claim 10 , wherein the RNA is in vitro transcribed RNA (IVT RNA).
12. The antigen-specific lymphoid cell of claim 4 , wherein the lymphoid cell is selected from the group consisting of a lymphocyte, lymphoblast and plasma cell.
13. The antigen-specific lymphoid cell of claim 4 , wherein the lymphoid cell is a T cell lacking endogenous expression of a T cell receptor.