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Article abstract

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

Andreatta M1 Karosiene E2 Rasmussen M3 Stryhn A3 Buus S3 Nielsen M1,4

Immunogenetics (2015)
DOI: 10.1007/s00251-015-0873-y

1Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín, CP(1650), San Martín, Buenos Aires, Argentina
2Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, 92037, USA
3Laboratory of Experimental Immunology, Faculty of Health Sciences, University of Copenhagen, DK-2200, Copenhagen, Denmark
4Center for Biological Sequence Analysis, Technical University of Denmark, DK-2800 Lyngby, Denmark

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

PMID: 26416257   [PDF]


Morten Nielsen,