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NetMHCpan, a Method for Quantitative Predictions of Peptide Binding to Any HLA-A and -B Locus Protein of Known Sequence.
Nielsen M1, Lundegaard C1, Blicher T1, Lamberth K2, Harndahl M2, Justesen S2, Roder G2, Peter B3, Sette A3, Lund O1 Buus S2
PLoSOne, 2(8): e796. doi:10.1371/journal.pone.0000796. 2007.

1Center for Biological Sequence Analysis, Technical University of Denmark, DK-2800 Lyngby, Denmark
2Division of Experimental Immunology, Institute of Medical Microbiology and Immunology, University of Copenhagen, Denmark
3La Jolla Institute for Allergy and Immunology, San Diego, California, United States of America

Binding of peptides to Major Histocompatibility Complex (MHC) molecules is the single most selective step in the recognition of pathogens by the cellular immune system. The human MHC class I system (HLA-I) is extremely polymorphic. The number of registered HLA-I molecules has now surpassed 1500. Characterizing the specificity of each separately would be a major undertaking.

Principal Findings
Here, we have drawn on a large database of known peptide-HLA-I interactions to develop a bioinformatics method, which takes both peptide and HLA sequence information into account, and generates quantitative predictions of the affinity of any peptide-HLA-I interaction. Prospective experimental validation of peptides predicted to bind to previously untested HLA-I molecules, cross-validation, and retrospective prediction of known HIV immune epitopes and endogenous presented peptides, all successfully validate this method. We further demonstrate that the method can be applied to perform a clustering analysis of MHC specificities and suggest using this clustering to select particularly informative novel MHC molecules for future biochemical and functional analysis.

Encompassing all HLA molecules, this high-throughput computational method lends itself to epitope searches that are not only genome- and pathogen-wide, but also HLA-wide. Thus, it offers a truly global analysis of immune responses supporting rational development of vaccines and immunotherapy. It also promises to provide new basic insights into HLA structure-function relationships. The method is available at NetMHCpan.

PLoSONE: Full text version
Full text including supplementary materials: PDF_fulltext.pdf


Morten Nielsen,