T cell receptor display

• Main Authors: JACOBSEN, BENT KARSTEN, BOULTER, JONATHAN MICHAEL, ANDERSEN, TORBEN BENT, MOLLOY, PETER EAMON, LI, YI
• Format: Patent
• Language: English
• Published: 26.09.2008
• Edition: 7
• Subjects: BEER; BIOCHEMISTRY; CHEMISTRY; COMBINATORIAL CHEMISTRY; COMPOSITIONS THEREOF; CULTURE MEDIA; ENZYMOLOGY; HUMAN NECESSITIES; HYGIENE; LIBRARIES, e.g. CHEMICAL LIBRARIES, IN SILICOLIBRARIES; MEDICAL OR VETERINARY SCIENCE; METALLURGY; MICROBIOLOGY; MICROORGANISMS OR ENZYMES; MUTATION OR GENETIC ENGINEERING; ORGANIC CHEMISTRY; PEPTIDES; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; SPIRITS; VINEGAR; WINE

Provided is a phage particle displaying on its surface a dimeric T-cell receptor (dTCR) polypeptide pair or single chain TCR (scTCR) polypeptide, the said dTCR polypeptide pair being constituted by a first polypeptide wherein a TCR alpha or delta chain variable domain sequence is fused to the N terminus of a TCR alpha chain constant domain extracellular sequence, and a second polypeptide wherein a TCR beta or gamma chain variable domain sequence is fused to the N terminus of a TCR beta chain constant domain extracellular sequence, the first and second polypeptides being linked by a disulfide bond which has no equivalent in native alpha beta or gamma delta T cell receptors; the said scTCR polypeptide being constituted by a first segment constituted by a TCR alpha or delta chain variable domain sequence fused to the N terminus of a TCR alpha chain constant domain extracellular sequence, a second segment constituted by a TCR beta or gamma chain variable domain fused to the N terminus of a TCR beta chain constant domain extracellular sequence, a linker sequence linking the C terminus of the first segment to the N terminus of the second segment, or vice versa, and a disulfide bond between the first and second segments, said disulfide bond being one which has no equivalent in native alpha beta or gamma delta T cell receptors; and wherein the said disulfide bond in the dTCR polypeptide pair or scTCR polypeptide is between pairs of cysteine residues substituted for specified amino acids in specific pairs of positions. Further provided are similar phage particles with truncated TCR, libraries of phage particles and methods of identification of TCRs using said libraries.