Antigen-specific t cell receptors and t cell epitopes

Abstract

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 - 11 . (canceled) 
     
     
         12 . A pharmaceutical composition comprising a cell comprising a nucleic acid encoding a T cell receptor α-chain or a T cell receptor comprising said T cell receptor α-chain,
 wherein said T cell receptor α-chain is selected from the group consisting of: 
 (i) a T cell receptor α-chain comprising at least one CDR sequences of a T cell receptor α-chain sequence selected from SEQ ID NOs: 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 140, 142, 144, 146, 148, 150, 152, 154, 156, 158, 160, 162, 164, 166, 168, 170, 176, 188, 190, 192, and 194 or a variant thereof and 
 (ii) a T cell receptor α-chain comprising a T cell receptor α-chain sequence selected from SEQ ID NOs: 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 140, 142, 144, 146, 148, 150, 152, 154, 156, 158, 160, 162, 164, 166, 168, 170, 176, 188, 190, 192, and 194 or a variant thereof. 
 
     
     
         13 . A pharmaceutical composition comprising a cell comprising a nucleic acid encoding a T cell receptor β-chain or a T cell receptor comprising said T cell receptor β-chain,
 wherein said T cell receptor β-chain is selected from the group consisting of: 
 (i) a T cell receptor β-chain comprising at least one CDR sequence of a T cell receptor β-chain sequence selected from SEQ ID NOs: 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 141, 143, 145, 147, 149, 151, 153, 155, 157, 159, 161, 163, 165, 167, 169, 171, 177, 189, 191, 193, and 195 or a variant thereof 
 and 
 (ii) a T cell receptor β-chain comprising a T cell receptor β-chain sequence selected from SEQ ID NOs: 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 141, 143, 145, 147, 149, 151, 153, 155, 157, 159, 161, 163, 165, 167, 169, 171, 177, 189, 191, 193, and 195 or a variant thereof. 
 
     
     
         14 . A pharmaceutical composition comprising a cell comprising 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 at least one CDR sequence of the T cell receptor α-chain sequence of SEQ ID NO: x or a variant thereof, and 
 (ii) a T cell receptor β-chain comprising at least one CDR sequences of a T cell receptor β-chain sequence of SEQ ID NO: x+1 or a variant thereof; 
   wherein x is selected from 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 140, 142, 144, 146, 148, 150, 152, 154, 156, 158, 160, 162, 164, 166, 168, 170, 176, 188, 190, 192, and 194   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: x or a variant thereof, and 
 (ii) a T cell receptor β-chain comprising the T cell receptor β-chain sequence of SEQ ID NO: x+1 or a variant thereof, 
   wherein x is selected from 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 140, 142, 144, 146, 148, 150, 152, 154, 156, 158, 160, 162, 164, 166, 168, 170, 176, 188, 190, 192, and 194.   
     
     
         15 - 16 . (canceled) 
     
     
         17 . A method for inducing an immune response in a subject, comprising administering to the subject the pharmaceutical composition of  claim 12 . 
     
     
         18 - 20 . (canceled) 
     
     
         21 . A method for inducing an immune response in a subject, comprising administering to the subject the pharmaceutical composition of  claim 13 . 
     
     
         22 . A method for inducing an immune response in a subject, comprising administering to the subject the pharmaceutical composition of  claim 14 . 
     
     
         23 . The pharmaceutical composition of  claim 12 , wherein the nucleic acid is RNA. 
     
     
         24 . The pharmaceutical composition of  claim 13 , wherein the nucleic acid is RNA. 
     
     
         25 . The pharmaceutical composition of  claim 14 , wherein the nucleic acid is RNA. 
     
     
         26 . The pharmaceutical composition of  claim 23 , wherein the RNA is in vitro transcribed RNA (IVT RNA). 
     
     
         27 . The pharmaceutical composition of  claim 24 , wherein the RNA is in vitro transcribed RNA (IVT RNA). 
     
     
         28 . The pharmaceutical composition of  claim 25 , wherein the RNA is in vitro transcribed RNA (IVT RNA). 
     
     
         29 . The pharmaceutical composition of  claim 12 , wherein the cell is a lymphoid cell. 
     
     
         30 . The pharmaceutical composition of  claim 13 , wherein the cell is a lymphoid cell. 
     
     
         31 . The pharmaceutical composition of  claim 14 , wherein the cell is a lymphoid cell. 
     
     
         32 . The pharmaceutical composition of  claim 29 , wherein the lymphoid cell is a T cell. 
     
     
         33 . The pharmaceutical composition of  claim 30 , wherein the lymphoid cell is a T cell. 
     
     
         34 . The pharmaceutical composition of  claim 31 , wherein the lymphoid cell is a T cell.