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Removing T-cell epitopes with computational protein design

Author:
King, Chris, Garza, Esteban N., Mazor, Ronit, Linehan, Jonathan L., Pastan, Ira, Pepper, Marion, Baker, David
Source:
Proceedings of the National Academy of Sciences of the United States of America 2014 v.111 no.23 pp. 8577-8582
ISSN:
0027-8424
Subject:
Pseudomonas, T-lymphocytes, epitopes, exotoxins, humans, immune response, protein structure, therapeutics
Abstract:
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.
Agid:
1786200