Directed evolution of human T-cell receptors with picomolar affinities by phage display

✍ Scribed by Li, Yi; Moysey, Ruth; Molloy, Peter E; Vuidepot, Anne-Lise; Mahon, Tara; Baston, Emma; Dunn, Steven; Liddy, Nathaniel; Jacob, Jansen; Jakobsen, Bent K

• Book ID: 109908350
• Publisher: Nature Publishing Group
• Year: 2005
• Tongue: English
• Weight: 240 KB
• Volume: 23
• Category: Article
• ISSN: 1087-0156
• DOI: 10.1038/nbt1070

✦ Synopsis

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 approximately 1-100 muM. 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) tax(11-19) peptide-HLA-A(*)0201 complex and the NY-ESO-1(157-165) 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.