Accurate pan-specific prediction of peptide-MHC class II binding affinity with improved binding core identification.
Journal:
Immunogenetics
PMID:
26416257
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
Keywords
Algorithms
Amino Acid Sequence
Animals
Binding Sites
Cluster Analysis
Computational Biology
Databases, Protein
Epitopes
Histocompatibility Antigens Class II
Humans
Mice
Models, Molecular
Molecular Sequence Data
Neural Networks, Computer
Peptide Fragments
Protein Binding
Sequence Homology, Amino Acid