Accurate pan-specific prediction of peptide-MHC class II binding affinity with improved binding core identification

• Published in: Immunogenetics (New York) Vol. 67; no. 11-12; pp. 641 - 650
• Main Authors: Andreatta, Massimo, Karosiene, Edita, Rasmussen, Michael, Stryhn, Anette, Buus, Søren, Nielsen, Morten
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.11.2015; Springer Nature B.V
• Subjects: Algorithms; Allergology; Amino Acid Sequence; Amino acids; Animals; Antigens; Binding Sites; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cluster Analysis; Computational Biology - methods; Cytomegalovirus; Databases, Protein; Epitopes - immunology; Experimental methods; Gene Function; Histocompatibility Antigens Class II - chemistry; Histocompatibility Antigens Class II - immunology; Histocompatibility Antigens Class II - metabolism; Human Genetics; Humans; Identification; Immune system; Immunology; Lymphocytes; Mice; Models, Molecular; Molecular Sequence Data; Neural networks; Neural Networks (Computer); Original Paper; Peptide Fragments - chemistry; Peptide Fragments - metabolism; Peptides; Protein Binding; Research methodology; Sequence Homology, Amino Acid; T cell receptors; Denmark; La Jolla California; United States > US; T cell cross-reactivity; Binding core; MHC class II; Peptide binding; Peptide-MHC; Artificial neural networks
• DOI: 10.1007/s00251-015-0873-y
• ISSN: 0093-7711; 1432-1211

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 .