Directed evolution of human T-cell receptors with picomolar affinities by phage display
Directed evolution of human T-cell receptors with picomolar affinities by phage display
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DOI：
10.1038/nbt1070
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发表时间：
2005-03-01
影响因子：
46.9
通讯作者：
Boulter, JM
中科院分区：
文献类型：
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作者：
Li, Y;Moysey, R;Boulter, JM
几乎所有蛋白质（包括与疾病相关的蛋白质）衍生的肽都可以作为肽-人白细胞抗原 (pHLA) 复合物呈递在细胞表面。 T 细胞通过其克隆重排的 T 细胞受体 (TCR) 特异性识别 pHLA，其天然亲和力仅限于 1-100 mu M-1。在这里，我们描述了十种不同的人类 TCR 在噬菌体表面的展示，并通过非天然链间二硫键稳定 (2)。我们报告了针对两种不同 pHLA 的高亲和力 TCR 的定向进化：人类 T 细胞嗜淋巴细胞病毒 1 型 (HTLV-1)tax(11-19) 肽-HLA-A*0201 复合物(3) 和 NY-ESO-1(157-165) 肿瘤相关肽抗原-HLA-A*0201 复合物(4)，亲和力高达 2.5 分别为 nM 和 26 pM，我们证明了它们针对细胞表面 pHLA 的高特异性和敏感性。
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.