T cell receptor display
AssigneeImmunocore Limited
InventorsBent Karsten Jakobsen, Torben Bent Andersen, Peter Eamon Molloy, Yi Li, Jonathan Michael Boulter
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Abstract
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.
Claims11
A phage particle displaying on its surface a dimeric T cell receptor (TCR) polypeptide pair constituted by:
- a TCR α chain variable domain sequence fused to the N terminus of a TCR α chain constant domain extracellular sequence;
- and
- a TCR β chain variable domain sequence fused to the N terminus of a TCR β chain constant domain extracellular sequence,
- wherein the TCR α chain constant domain extracellular sequence and the TCR β chain constant domain extracellular sequence are linked by a disulfide bond between cysteine residues substituted for:
- Thr 48 of exon 1 of TRAC*01 and Ser 57 of exon 1 of TRBC1*01 or TRBC2*01;
- Thr 45 of exon 1 of TRAC*01 and Ser 77 of exon 1 of TRBC1*01 or TRBC2*01;
- Tyr 10 of exon 1 of TRAC*01 and Ser 17 of exon 1 of TRBC1*01 or TRBC2*01;
- Thr 45 of exon 1 of TRAC*01 and Asp 59 of exon 1 of TRBC1*01 or TRBC2*01;
- or
- Ser 15 of exon 1 of TRAC*01 and Glu 15 of exon 1 of TRBC1*01 or TRBC2*01.
A filamentous phage particle displaying on its surface a human dimeric T cell receptor (TCR) polypeptide pair constituted by:
- a TCR α chain variable domain sequence fused to the N terminus of a TCR α chain constant domain extracellular sequence;
- and
- a TCR β chain variable domain sequence fused to the N terminus of a TCR β chain constant domain extracellular sequence,
- wherein the TCR α chain constant domain extracellular sequence and the TCR β chain constant domain extracellular sequence are linked by a disulfide bond between cysteine residues substituted for Thr 48 of exon 1 of TRAC*01 and Ser 57 of exon 1 of TRBC1*01 or TRBC2*01, and wherein the C terminus of the TCR α chain constant domain extracellular sequence or the C terminus of the TCR β chain constant domain extracellular sequence is linked by a peptide bond to a coat protein of the phage particle.
A diverse library comprising a plurality of phage particles displaying on their surfaces dimeric T cell receptor (TCR) polypeptide pairs constituted by:
- a TCR α chain variable domain sequence fused to the N terminus of a TCR α chain constant domain extracellular sequence;
- and
- a TCR β chain variable domain sequence fused to the N terminus of a TCR β chain constant domain extracellular sequence,
- wherein the TCR α chain constant domain extracellular sequence and the TCR β chain constant domain extracellular sequence are linked by a disulfide bond between cysteine residues substituted for:
- Thr 48 of exon 1 of TRAC*01 and Ser 57 of exon 1 of TRBC1*01 or TRBC2*01;
- Thr 45 of exon 1 of TRAC*01 and Ser 77 of exon 1 of TRBC1*01 or TRBC2*01;
- Tyr 10 of exon 1 of TRAC*01 and Ser 17 of exon 1 of TRBC1*01 or TRBC2*01;
- Thr 45 of exon 1 of TRAC*01 and Asp 59 of exon 1 of TRBC1*01 or TRBC2*01;
- or
- Ser 15 of exon 1 of TRAC*01 and Glu 15 of exon 1 of TRBC1*01 or TRBC2*01.
Dependencies are inferred from the claim text.