title: Pan-Specific Prediction of Peptide-MHC Class I Complex Stability, a Correlate of T Cell Immunogenicity.
abstract: 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.
authors.affiliation: Laboratory of Experimental Immunology, Department of International Health, Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 N Copenhagen, Denmark;
authors.forename: Michael
authors.initials: M
authors.lastname: Rasmussen
authors.affiliation: Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín, San Martín, B 1650 HMP, Buenos Aires, Argentina; and.
authors.forename: Emilio
authors.identifier: 0000-0001-9121-7149
authors.initials: E
authors.lastname: Fenoy
authors.affiliation: Laboratory of Experimental Immunology, Department of International Health, Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 N Copenhagen, Denmark;
authors.forename: Mikkel
authors.initials: M
authors.lastname: Harndahl
authors.affiliation: Laboratory of Experimental Immunology, Department of International Health, Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 N Copenhagen, Denmark;
authors.forename: Anne Bregnballe
authors.initials: AB
authors.lastname: Kristensen
authors.affiliation: Laboratory of Experimental Immunology, Department of International Health, Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 N Copenhagen, Denmark;
authors.forename: Ida Kallehauge
authors.identifier: 0000-0003-0791-8925
authors.initials: IK
authors.lastname: Nielsen
authors.affiliation: Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín, San Martín, B 1650 HMP, Buenos Aires, Argentina; and Center for Biological Sequence Analysis, Technical University of Denmark, 2800 Kongens Lyngby, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Nielsen
authors.affiliation: Laboratory of Experimental Immunology, Department of International Health, Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 N Copenhagen, Denmark; sbuus@sund.ku.dk.
authors.forename: Søren
authors.identifier: 0000-0001-8363-1999
authors.initials: S
authors.lastname: Buus
mesh_terms: D017951:Antigen Presentation / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D016571:Neural Networks, Computer; D010455:Peptides / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D055550:Protein Stability
chemical_list: D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D010455:Peptides