title: Accurate pan-specific prediction of peptide-MHC class II binding affinity with improved binding core identification.
abstract: A key event in the generation of a cellular response against malicious organisms through the endocytic pathway is binding of peptidic antigens by major histocompatibility complex class II (MHC class II) molecules. The bound peptide is then presented on the cell surface where it can be recognized by T helper lymphocytes. NetMHCIIpan is a state-of-the-art method for the quantitative prediction of peptide binding to any human or mouse MHC class II molecule of known sequence. In this paper, we describe an updated version of the method with improved peptide binding register identification. Binding register prediction is concerned with determining the minimal core region of nine residues directly in contact with the MHC binding cleft, a crucial piece of information both for the identification and design of CD4(+) T cell antigens. When applied to a set of 51 crystal structures of peptide-MHC complexes with known binding registers, the new method NetMHCIIpan-3.1 significantly outperformed the earlier 3.0 version. We illustrate the impact of accurate binding core identification for the interpretation of T cell cross-reactivity using tetramer double staining with a CMV epitope and its variants mapped to the epitope binding core. NetMHCIIpan is publicly available at http://www.cbs.dtu.dk/services/NetMHCIIpan-3.1 .
authors.affiliation: Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín, CP(1650), San Martín, Buenos Aires, Argentina.
authors.forename: Massimo
authors.initials: M
authors.lastname: Andreatta
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, 92037, USA.
authors.forename: Edita
authors.initials: E
authors.lastname: Karosiene
authors.affiliation: Laboratory of Experimental Immunology, Faculty of Health Sciences, University of Copenhagen, DK-2200, Copenhagen, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Rasmussen
authors.affiliation: Laboratory of Experimental Immunology, Faculty of Health Sciences, University of Copenhagen, DK-2200, Copenhagen, Denmark.
authors.forename: Anette
authors.initials: A
authors.lastname: Stryhn
authors.affiliation: Laboratory of Experimental Immunology, Faculty of Health Sciences, University of Copenhagen, DK-2200, Copenhagen, Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Buus
authors.affiliation: Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín, CP(1650), San Martín, Buenos Aires, Argentina. mniel@cbs.dtu.dk.|Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, DK-2800, Lyngby, Denmark. mniel@cbs.dtu.dk.
authors.forename: Morten
authors.initials: M
authors.lastname: Nielsen
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods*; D030562:Databases, Protein; D000939:Epitopes / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016571:Neural Networks, Computer; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid
chemical_list: D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments
keywords: Artificial neural networks; Binding core; MHC class II; Peptide binding; Peptide-MHC; T cell cross-reactivity