Pan-specific prediction of peptide-MHC Class I complex stability, a correlate of T cell immunogenicity

Authors
Rasmussen, Michael; Fenoy, Luis Emilio; Harndahl, Mikkel; Kristensen, Anne Bregnballe; Nielsen, Ida Kallehauge; Nielsen, Morten; Buus, Søren
Publication Year
2016
Language
English
Format
article
Status
Published version
Description
Binding of peptides to MHC class I (MHC-I) molecules is the most selective event in the processing and presentation of Ags to CTL, and insights into the mechanisms that govern peptide-MHC-I binding should facilitate our understanding of CTL biology. Peptide-MHC-I interactions have traditionally been quantified by the strength of the interaction, that is, the binding affinity, yet it has been shown that the stability of the peptide-MHC-I complex is a better correlate of immunogenicity compared with binding affinity. In this study, we have experimentally analyzed peptide-MHC-I complex stability of a large panel of human MHC-I allotypes and generated a body of data sufficient to develop a neural network-based pan-specific predictor of peptide-MHC-I complex stability. Integrating the neural network predictors of peptide-MHC-I complex stability with state-of-the-art predictors of peptide-MHC-I binding is shown to significantly improve the prediction of CTL epitopes. The method is publicly available at http://www.cbs.dtu.dk/services/NetMHCstabpan.
Fil: Rasmussen, Michael. Universidad de Copenhagen; Dinamarca
Fil: Fenoy, Luis Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas ; Argentina
Fil: Harndahl, Mikkel. Universidad de Copenhagen; Dinamarca
Fil: Kristensen, Anne Bregnballe. Universidad de Copenhagen; Dinamarca
Fil: Nielsen, Ida Kallehauge. Universidad de Copenhagen; Dinamarca
Fil: Nielsen, Morten. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Copenhagen; Dinamarca
Fil: Buus, Søren. Universidad de Copenhagen; Dinamarca
Subject
MHC-I
STABILITY
PREDICTOR
IMMUNOLOGY
Ciencias de la Computación
Ciencias de la Computación e Información
CIENCIAS NATURALES Y EXACTAS
Access level
Restricted access
License
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repository
CONICET Digital (CONICET)
Institution
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identifier
oai:ri.conicet.gov.ar:11336/49514