title: Class I T-cell epitope prediction: improvements using a combination of proteasome cleavage, TAP affinity, and MHC binding.
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.
authors.affiliation: The Edward Jenner Institute for Vaccine Research, Compton RG20 7NN, UK.
authors.forename: Irini A
authors.initials: IA
authors.lastname: Doytchinova
authors.forename: Darren R
authors.initials: DR
authors.lastname: Flower
mesh_terms: D018528:ATP-Binding Cassette Transporters; D000465:Algorithms; D000818:Animals; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015234:HLA-A Antigens / Q000276:immunology*; D015235:HLA-B Antigens / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D008954:Models, Biological; D011237:Predictive Value of Tests; D046988:Proteasome Endopeptidase Complex / Q000276:immunology*; D020539:Sequence Analysis, Protein
chemical_list: D018528:ATP-Binding Cassette Transporters; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015395:Histocompatibility Antigens Class I; C477327:transporter associated with antigen processing (TAP); D046988:Proteasome Endopeptidase Complex