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- Title
Directed evolution of human T-cell receptors with picomolar affinities by phage display.
- Authors
Yi Li; Moysey, Ruth; Molloy, Peter E; Vuidepot, Anne-Lise; Mahon, Tara; Baston, Emma; Dunn, Steven; Liddy, Nathaniel; Jacob, Jansen; Jakobsen, Bent K; Boulter, Jonathan M
- Abstract
Peptides derived from almost all proteins, including disease-associated proteins, can be presented on the cell surface as peptide-human leukocyte antigen (pHLA) complexes. T cells specifically recognize pHLA with their clonally rearranged T-cell receptors (TCRs), whose natural affinities are limited to~1-100µM. Here we describe the display of ten different human TCRs on the surface of bacteriophage, stabilized by a nonnative interchain disulfide bond. We report the directed evolution of high-affinity TCRs specific for two different pHLAs: the human T-cell lymphotropic virus type 1 (HTLV-1) tax11-19 peptide-HLA-A*0201 complex and the NY-ESO-1157-165 tumor-associated peptide antigen-HLA-A*0201 complex, with affinities of up to 2.5 nM and 26 pM, respectively, and we demonstrate their high specificity and sensitivity for targeting of cell-surface pHLAs.
- Publication
Nature Biotechnology, 2005, Vol 23, Issue 3, p349
- ISSN
1087-0156
- Publication type
Academic Journal
- DOI
10.1038/nbt1070