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. 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: 44 and a nucleic acid encoding a T cell receptor β-chain comprising the T cell receptor β-chain sequence of SEQ ID NO: 45 or (ii) a nucleic acid encoding a T cell receptor comprising the T cell receptor α-chain sequence of SEQ ID NO: 44 and the T cell receptor β-chain sequence of SEQ ID NO: 45.
2. A pharmaceutical composition comprising the antigen-specific lymphoid cell of claim 1 .
3. 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: 44 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: 45 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: 44 and all three of the CDR sequences the T cell receptor β-chain sequence of SEQ ID NO: 45.
4. A pharmaceutical composition comprising the antigen-specific lymphoid cell of claim 3 .
5. The antigen-specific lymphoid cell of claim 1 , wherein the nucleic acid is RNA.
6. The antigen-specific lymphoid cell of claim 5 , wherein the RNA is in vitro transcribed RNA (IVT RNA).
7. The antigen-specific lymphoid cell of claim 1 , wherein the lymphoid cell is selected from the group consisting of a lymphocyte, lymphoblast and plasma cell.
8. The antigen-specific lymphoid cell of claim 1 , wherein the lymphoid cell is a T cell lacking endogenous expression of a T cell receptor.
9. The antigen-specific lymphoid cell of claim 3 , wherein the nucleic acid is RNA.
10. The antigen-specific lymphoid cell of claim 9 , wherein the RNA is in vitro transcribed RNA (IVT RNA).
11. The antigen-specific lymphoid cell of claim 3 , wherein the lymphoid cell is selected from the group consisting of a lymphocyte, lymphoblast and plasma cell.
12. The antigen-specific lymphoid cell of claim 3 , wherein the lymphoid cell is a T cell lacking endogenous expression of a T cell receptor.