Improved methods for predicting peptide binding affinity to MHC class II molecules

Immunology. 2018 Jul;154(3):394-406. doi: 10.1111/imm.12889. Epub 2018 Feb 6.


Major histocompatibility complex class II (MHC-II) molecules are expressed on the surface of professional antigen-presenting cells where they display peptides to T helper cells, which orchestrate the onset and outcome of many host immune responses. Understanding which peptides will be presented by the MHC-II molecule is therefore important for understanding the activation of T helper cells and can be used to identify T-cell epitopes. We here present updated versions of two MHC-II-peptide binding affinity prediction methods, NetMHCII and NetMHCIIpan. These were constructed using an extended data set of quantitative MHC-peptide binding affinity data obtained from the Immune Epitope Database covering HLA-DR, HLA-DQ, HLA-DP and H-2 mouse molecules. We show that training with this extended data set improved the performance for peptide binding predictions for both methods. Both methods are publicly available at and

Keywords: MHC binding specificity; T-cell epitope; affinity predictions; immunogenic peptides; peptide-MHC binding.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Computational Biology / methods*
  • Databases, Protein
  • Epitope Mapping / methods*
  • Epitopes / immunology*
  • Epitopes / metabolism
  • Epitopes, T-Lymphocyte / chemistry
  • Epitopes, T-Lymphocyte / immunology
  • Histocompatibility Antigens Class II / immunology*
  • Histocompatibility Antigens Class II / metabolism
  • Humans
  • Oligopeptides / chemistry
  • Oligopeptides / immunology*
  • Oligopeptides / metabolism
  • Protein Binding
  • Reproducibility of Results


  • Epitopes
  • Epitopes, T-Lymphocyte
  • Histocompatibility Antigens Class II
  • MHC binding peptide
  • Oligopeptides