Removing T-cell epitopes with computational protein design

King, C. et al. PNAS 111, 8577-82 (2014)

Immune reposes can make protein therapeutics ineffective or even dangerous. Here 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.