Poor correlation between T-cell activation assays and HLA-DR binding prediction algorithms in an immunogenic fragment of Pseudomonas exotoxin A

Poor correlation between T-cell activation assays and HLA-DR binding prediction algorithms in an... The ability to identify immunogenic determinants that activate T-cells is important for the development of new vaccines, allergy therapy and protein therapeutics. In silico MHC-II binding prediction algorithms are often used for T-cell epitope identification. To understand how well those programs predict immunogenicity, we computed HLA binding to peptides spanning the sequence of PE38, a fragment of an anti-cancer immunotoxin, and compared the predicted and experimentally identified T-cell epitopes. We found that the prediction for individual donors did not correlate well with the experimental data. Furthermore, prediction of T-cell epitopes in an HLA heterogenic population revealed that the two strongest epitopes were predicted at multiple cutoffs but the third epitope was predicted negative at all cutoffs and overall 4/9 epitopes were missed at several cutoffs. We conclude that MHC class-II binding predictions are not sufficient to predict the T-cell epitopes in PE38 and should be supplemented by experimental work. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Immunological Methods Elsevier

Poor correlation between T-cell activation assays and HLA-DR binding prediction algorithms in an immunogenic fragment of Pseudomonas exotoxin A

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Publisher
Elsevier
Copyright
Copyright © 2015 Elsevier Ltd
ISSN
0022-1759
D.O.I.
10.1016/j.jim.2015.06.003
Publisher site
See Article on Publisher Site

Abstract

The ability to identify immunogenic determinants that activate T-cells is important for the development of new vaccines, allergy therapy and protein therapeutics. In silico MHC-II binding prediction algorithms are often used for T-cell epitope identification. To understand how well those programs predict immunogenicity, we computed HLA binding to peptides spanning the sequence of PE38, a fragment of an anti-cancer immunotoxin, and compared the predicted and experimentally identified T-cell epitopes. We found that the prediction for individual donors did not correlate well with the experimental data. Furthermore, prediction of T-cell epitopes in an HLA heterogenic population revealed that the two strongest epitopes were predicted at multiple cutoffs but the third epitope was predicted negative at all cutoffs and overall 4/9 epitopes were missed at several cutoffs. We conclude that MHC class-II binding predictions are not sufficient to predict the T-cell epitopes in PE38 and should be supplemented by experimental work.

Journal

Journal of Immunological MethodsElsevier

Published: Oct 1, 2015

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