Institute for Protein Design, Department of Biochemistry and
Department of Immunology, University of Washington, Seattle, WA 98195; and.
Proc Natl Acad Sci U S A. 2014 Jun 10;111(23):8577-82. doi: 10.1073/pnas.1321126111. Epub 2014 May 19.
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.
免疫反应会使蛋白质疗法失效甚至危险。我们描述了一种通用的计算蛋白质设计方法，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，同时不破坏蛋白质结构和功能，从而降低免疫原性。我们表明，该方法再现了先前关于降低免疫原性的实验结果，并且我们使用它在不破坏功能的情况下破坏 GFP 和假单胞菌外毒素 A 中的 T 细胞表位。
