학술논문

Pan-Specific Prediction of Peptide-MHC Class I Complex Stability, a Correlate of T Cell Immunogenicity.
Document Type
Academic Journal
Author
Rasmussen M; Laboratory of Experimental Immunology, Department of International Health, Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 N Copenhagen, Denmark;; Fenoy E; Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín, San Martín, B 1650 HMP, Buenos Aires, Argentina; and.; Harndahl M; Laboratory of Experimental Immunology, Department of International Health, Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 N Copenhagen, Denmark;; Kristensen AB; Laboratory of Experimental Immunology, Department of International Health, Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 N Copenhagen, Denmark;; Nielsen IK; Laboratory of Experimental Immunology, Department of International Health, Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 N Copenhagen, Denmark;; Nielsen M; 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.; Buus S; 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.
Source
Publisher: American Association of Immunologists Country of Publication: United States NLM ID: 2985117R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1550-6606 (Electronic) Linking ISSN: 00221767 NLM ISO Abbreviation: J Immunol Subsets: MEDLINE
Subject
Language
English
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.
(Copyright © 2016 by The American Association of Immunologists, Inc.)