Details

Autor(en) / Beteiligte

• Nielsen, Morten
• Lundegaard, Claus
• Blicher, Thomas
• Lamberth, Kasper
• Harndahl, Mikkel
• Justesen, Sune
• Røder, Gustav
• Peters, Bjoern
• Sette, Alessandro
• Lund, Ole
• Buus, Søren
• Kallas, Esper

Titel

NetMHCpan, a method for quantitative predictions of peptide binding to any HLA-A and -B locus protein of known sequence

Ist Teil von

• PloS one, 2007-08, Vol.2 (8), p.e796-e796

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2007

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. 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 http://www.cbs.dtu.dk/services/NetMHCpan.