title: T-cell epitope prediction: rescaling can mask biological variation between MHC molecules.
abstract: Theoretical methods for predicting CD8+ T-cell epitopes are an important tool in vaccine design and for enhancing our understanding of the cellular immune system. The most popular methods currently available produce binding affinity predictions across a range of MHC molecules. In comparing results between these MHC molecules, it is common practice to apply a normalization procedure known as rescaling, to correct for possible discrepancies between the allelic predictors. Using two of the most popular prediction software packages, NetCTL and NetMHC, we tested the hypothesis that rescaling removes genuine biological variation from the predicted affinities when comparing predictions across a number of MHC molecules. We found that removing the condition of rescaling improved the prediction software's performance both qualitatively, in terms of ranking epitopes, and quantitatively, in the accuracy of their binding affinity predictions. We suggest that there is biologically significant variation among class 1 MHC molecules and find that retention of this variation leads to significantly more accurate epitope prediction.
authors.affiliation: Department of Immunology, Imperial College School of Medicine, London, United Kingdom. aidan.macnamara@ic.ac.uk
authors.forename: Aidan
authors.initials: A
authors.lastname: MacNamara
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kadolsky
authors.forename: Charles R M
authors.initials: CR
authors.lastname: Bangham
authors.forename: Becca
authors.initials: B
authors.lastname: Asquith
mesh_terms: D000465:Algorithms; D003198:Computer Simulation; D018604:Epitope Mapping / Q000379:methods*; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry* / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000276:immunology*; D008956:Models, Chemical; D008958:Models, Molecular; D025941:Protein Interaction Mapping / Q000379:methods*; D013601:T-Lymphocytes / Q000737:chemistry* / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte