Removing T-cell epitopes with computational protein design
Removing T-cell epitopes with computational protein design
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DOI：
10.1073/pnas.1321126111
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发表时间：
2014-06-10
影响因子：
11.1
通讯作者：
Baker, David
中科院分区：
文献类型：
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作者：
King, Chris;Garza, Esteban N.;Baker, David
免疫反应会使蛋白质疗法无效甚至危险。我们描述了一种通用计算蛋白设计方法，用于通过消除已知和预测的T细胞表位并最大化人类肽序列的含量而不会破坏蛋白质结构和功能，从而降低免疫原性。我们表明，该方法概括了先前有关降低免疫原性的实验结果，并且我们使用它来破坏GFP和假单胞菌外毒素A中的T细胞表位，而不会破坏功能。
Immune responses can make protein therapeutics ineffective or even dangerous. We describe a general computational protein design method for reducing immunogenicity by eliminating known and predicted T-cell epitopes and maximizing the content of human peptide sequences without disrupting protein structure and function. We show that the method recapitulates previous experimental results on immunogenicity reduction, and we use it to disrupt T-cell epitopes in GFP and Pseudomonas exotoxin A without disrupting function.