TCR LIBRARIES

1 . A library of particles, the library displaying a plurality of different T cell receptors (TCRs), wherein the plurality of TCRs consists essentially of TCRs comprising an alpha chain comprising an alpha chain variable domain and a beta chain comprising a beta chain variable domain, wherein the alpha chain variable domain comprises a TRAV27 gene product and the beta chain variable domain comprises a TRBV9 gene product.

2 . The library according to claim 1 wherein the CDR3 sequence of the alpha and/or beta chain variable domains are obtained from a natural repertoire.

3 . The library according to claim 1 or claim 2 , wherein the CDR3 sequence of the alpha and/or beta chain variable domains is designed artificially.

4 . The library according to any one of claims 1 to 3 , wherein the framework region, CDR1, CDR2 and/or CDR3 sequence of the alpha and/or beta variable domain comprises a non-natural mutation a non-natural mutation.

5 . The library according to any one of claims 1 to 4 , wherein the alpha chain variable domain and the beta chain variable domain are displayed as a single polypeptide chain.

6 . The library according to any one of claims 1 to 4 wherein the TCRs comprise a non-native disulphide bond between a constant region of the alpha chain and a constant region of the beta chain.

7 . The library according to any one claims 1 to 4 wherein the TCRs comprise a native disulphide bond between a constant region of the alpha chain and a constant region of the beta chain.

8 . The library according to any one of claims 1 to 4 , wherein each alpha chain and each beta chain comprises a dimerization domain.

9 . The library according to claim 8 , wherein the dimerization domain is heterologous.

10 . The library according to any one of claims 1 to 9 wherein the particles are phage particles.

11 . The library according to any one of claims 1 to 9 wherein the particles are ribosomes.

12 . The library according to any one of claims 1 to 9 wherein the particles are yeast cells.

13 . The library according to any one of claims 1 to 9 wherein the particles are mammalian cells.

14 . A non-natural isolated T cell receptor (TCR) comprising a TCR alpha chain variable domain comprising a TRAV27 gene product and a TCR beta chain variable domain comprising a TRBV9 gene product obtained from a library according to any one of claims 1 to 13 .

15 . The TCR according to claim 14 , wherein the TCR is soluble.

16 . Use of a library according to any one of claims 1 to 13 , to identify a TCR that specifically binds to a peptide antigen.

17 . A method of obtaining a T cell receptor that specifically binds a peptide antigen, comprising screening the library of any one of claims 1 to 13 with the peptide antigen, the method comprising:

a) panning the library using as a target the peptide antigen;

b) repeating step a) one or more times;

c) screening the phage clones identified in step a) or b); and

d) identifying a TCR that specifically binds the peptide antigen.

18 . A nucleic acid encoding a TCR alpha chain variable domain and/or a beta chain variable domain of the TCR according to claim 14 or claim 15 .

19 . A method of making a library of particles, the library displaying a plurality of different TCRs, the method comprising:

i) obtaining a plurality of nucleic acids that encode different TRAV27 alpha chain variable domains;

ii) obtaining a plurality of nucleic acids that encode different TRBV9 beta chain variable domains;

iii) cloning the TRAV27 alpha chain variable domain encoding nucleic acids into expression vectors;

iv) cloning the TRBV9 beta chain variable domain encoding nucleic acids into the same or different vectors; and

v) expressing the vectors in particles, thereby generating a library consisting essentially of TCRs comprising an alpha chain variable domain and a beta chain variable domain encoded by the nucleic acids.

20 . A method of making a library of particles, the library displaying a plurality of different TCRs, the method comprising:

i) obtaining a plurality of nucleic acids that encode different TRAV27 alpha chain variable domains using primers that hybridise to nucleic acids encoding TRAV27 alpha chain variable domains;

ii) obtaining a plurality of nucleic acids that encode different TRBV9 beta chain variable domains using primers that hybridise to nucleic acids encoding TRBV9 beta chain variable domains;

iii) cloning the TRAV27 alpha chain variable domain encoding nucleic acids into expression vectors;

iv) cloning the TRBV9 beta chain variable domain encoding nucleic acids into the same or different vectors; and

v) expressing the vectors in particles, thereby generating a library consisting essentially of TCRs comprising an alpha chain variable domain and a beta chain variable domain encoded by the nucleic acids to which said primers hybridise.

21 . The method of claim 19 , wherein all or part of each of the plurality of nucleic acids encoding TRAV27 or TRVB9, in step (i) and/or step (ii) is obtained synthetically.

22 . The method of claim 19 , wherein all or part of each of the plurality of nucleic acids encoding TRAV27 or TRVB9, in step (i) and/or step (ii) is designed artificially.

23 . The method of anyone of claims 19 to 22 , wherein all or part of the framework region, CDR1, CDR2 and/or CDR3 is obtained synthetically and/or artificially designed.

24 . The method of claim 19 or claim 20 , wherein at least the CDR3 sequence of the nucleic acids of step (i) and step (ii) are obtained from a natural repertoire.

25 . The method of any one of claims 19 to 24 , comprising a further step of introducing non-natural mutations to one or more of nucleic acids.

26 . The method of claim 25 , wherein non-natural mutations are introduced to one or more of nucleic acids prior to step iii).

27 . A method according to any one of claims 19 to 26 , wherein the TCR alpha chain variable domain and the TCR beta chain variable domain are expressed as a single chain polypeptide.

28 . The method of obtaining a T cell receptor that specifically binds a peptide antigen, comprising screening the library according to any one of claims 1 to 13 with the peptide antigen.

29 . The method of claim 28 , wherein the peptide antigen comprises HLA-A2

30 . A particle displaying on its surface a TCR according to claim 14 or claim 15 .

31 . The particle according to claim 30 , wherein the particle is a phage particle, a ribosome, a yeast cell or a mammalian cell.