Class I T-cell epitope prediction: improvements using a combination of proteasome cleavage, TAP affinity, and MHC binding

Irini A. Doytchinova, Darren R. Flower

Research output: Contribution to journalArticle

Abstract

Cleavage by the proteasome is responsible for generating the C terminus of T-cell epitopes. Modeling the process of proteasome cleavage as part of a multi-step algorithm for T-cell epitope prediction will reduce the number of non-binders and increase the overall accuracy of the predictive algorithm. Quantitative matrix-based models for prediction of the proteasome cleavage sites in a protein were developed using a training set of 489 naturally processed T-cell epitopes (nonamer peptides) associated with HLA-A and HLA-B molecules. The models were validated using an external test set of 227 T-cell epitopes. The performance of the models was good, identifying 76% of the C-termini correctly. The best model of proteasome cleavage was incorporated as the first step in a three-step algorithm for T-cell epitope prediction, where subsequent steps predicted TAP affinity and MHC binding using previously derived models.
Original languageEnglish
Pages (from-to)2037-2044
Number of pages8
JournalMolecular Immunology
Volume43
Issue number13
Early online date9 Mar 2006
DOIs
Publication statusPublished - May 2006

Keywords

  • proteasome cleavage
  • epitope
  • additive method

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