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

被引：348

作者：

Li, Y ^{[1
]}

Moysey, R ^{[1
]}

Molloy, PE ^{[1
]}

Vuidepot, AL ^{[1
]}

Mahon, T ^{[1
]}

Baston, E ^{[1
]}

Dunn, S ^{[1
]}

Liddy, N ^{[1
]}

Jacob, J ^{[1
]}

Jakobsen, BK ^{[1
]}

Boulter, JM ^{[1
]}

机构：

[1] Avidex Ltd, Abingdon OX14 4RX, Oxon, England

来源：

NATURE BIOTECHNOLOGY | 2005年 / 23卷 / 03期

关键词：

D O I：

10.1038/nbt1070

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

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 similar to 1-100 mu M-1. Here we describe the display of ten different human TCRs on the surface of bacteriophage, stabilized by a nonnative interchain disulfide bond(2). 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(3) and the NY-ESO-1(157-165) tumor-associated peptide antigen-HLA-A*0201 complex(4), 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.

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页码：349 / 354

页数：6

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