T cell receptor display
A proteinaceous particle, for example a bacteriophage, ribosome or cell, displaying on its surface a T-cell receptor (TCR). The displayed TCR is preferably a heterodimer having a non-native disulfide bond between constant domain residues. Such display particles may be used for the creation of diverse TCR libraries for the identification of high affinity TCRs. Several high affinities are disclosed.
1. A phage particle displaying on its surface a dimeric T-cell receptor (dTCR) polypeptide pair, wherein the dTCR polypeptide pair comprises
a first polypeptide wherein a TCR α or δ chain variable domain sequence is fused to N
terminus of a TCR αchain constant domain extracellular sequence, and
a second polypeptide wherein a TCR β or γ chain variable domain sequence is fused to N
terminus of a TCR β chain constant domain extracellular sequence,
wherein the first and second polypeptides are linked by a disulfide bond which corresponds to a native inter-chain disulfide bond present in native dimeric αβ TCRs.
2. The phage particle of claim 1 wherein the phage particle is a filamentous phage particle.
3. The phage particle of claim 1 or claim 2 wherein C-terminus of one member of the dTCR polypeptide pair is linked by a peptide bond to a surface exposed residue of the phage particle.
4. A diverse library of phage particles as claimed in claim 1 .
5. The diverse library of claim 4 wherein diversity resides in the variable domain(s) of the dTCR polypeptide pair.
6. A method for identifying TCRs with a specific characteristic comprising subjecting the diverse library of phage particles displaying TCRs of claim 4 or claim 5 to
a selection process comprising selecting for the characteristic, and isolating phage particles which display a TCR having the characteristic, and optionally to an amplification process to multiply the isolated particles and/or
a screening process comprising measuring for the characteristic, identifying phage particles displaying a TCR with the characteristic and isolating the phage particles, and
optionally to an amplification process to multiply the isolated particles.
7. The method of claim 6 wherein the specific characteristic is increased affinity for a TCR ligand.
8. A diverse library of phage particles as claimed in claim 2 .
9. The diverse library of claim 8 wherein diversity resides in the variable domain(s) of the dTCR polypeptide pair.
10. A diverse library of phage particles as claimed in claim 3 .
11. The diverse library of claim 10 wherein diversity resides in the variable domain(s) of the dTCR polypeptide pair.