title: Scrutinizing MHC-I binding peptides and their limits of variation.
abstract: Designed peptides that bind to major histocompatibility protein I (MHC-I) allomorphs bear the promise of representing epitopes that stimulate a desired immune response. A rigorous bioinformatical exploration of sequence patterns hidden in peptides that bind to the mouse MHC-I allomorph H-2K(b) is presented. We exemplify and validate these motif findings by systematically dissecting the epitope SIINFEKL and analyzing the resulting fragments for their binding potential to H-2K(b) in a thermal denaturation assay. The results demonstrate that only fragments exclusively retaining the carboxy- or amino-terminus of the reference peptide exhibit significant binding potential, with the N-terminal pentapeptide SIINF as shortest ligand. This study demonstrates that sophisticated machine-learning algorithms excel at extracting fine-grained patterns from peptide sequence data and predicting MHC-I binding peptides, thereby considerably extending existing linear prediction models and providing a fresh view on the computer-based molecular design of future synthetic vaccines. The server for prediction is available at http://modlab-cadd.ethz.ch (SLiDER tool, MHC-I version 2012).
authors.affiliation: ETH Zürich, Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Zürich, Switzerland.
authors.forename: Christian P
authors.initials: CP
authors.lastname: Koch
authors.forename: Anna M
authors.initials: AM
authors.lastname: Perna
authors.forename: Max
authors.initials: M
authors.lastname: Pillong
authors.forename: Nickolay K
authors.initials: NK
authors.lastname: Todoroff
authors.forename: Paul
authors.initials: P
authors.lastname: Wrede
authors.forename: Gerd
authors.initials: G
authors.lastname: Folkers
authors.forename: Jan A
authors.initials: JA
authors.lastname: Hiss
authors.forename: Gisbert
authors.initials: G
authors.lastname: Schneider
mesh_terms: D000818:Animals; D001185:Artificial Intelligence; D019295:Computational Biology; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D051379:Mice; D010455:Peptides / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D015395:Histocompatibility Antigens Class I; D010455:Peptides