title: Exhaustive proteome mining for functional MHC-I ligands.
abstract: We present the development and application of a new machine-learning approach to exhaustively and reliably identify major histocompatibility complex class I (MHC-I) ligands among all 20(8) octapeptides and in genome-derived proteomes of Mus musculus , influenza A H3N8, and vesicular stomatitis virus (VSV). Focusing on murine H-2K(b), we identified potent octapeptides exhibiting direct MHC-I binding and stabilization on the surface of TAP-deficient RMA-S cells. Computationally identified VSV-derived peptides induced CD8(+) T-cell proliferation after VSV-infection of mice. The study demonstrates that high-level machine-learning models provide a unique access to rationally designed peptides and a promising approach toward "reverse vaccinology".
authors.affiliation: Department of Chemistry and Applied Biosciences, Eidgenössische Technische Hochschule (ETH) , Wolfgang-Pauli-Str. 10, 8093 Zürich, Switzerland.
authors.forename: Christian P
authors.initials: CP
authors.lastname: Koch
authors.forename: Anna M
authors.initials: AM
authors.lastname: Perna
authors.forename: Sabrina
authors.initials: S
authors.lastname: Weissmüller
authors.forename: Stefanie
authors.initials: S
authors.lastname: Bauer
authors.forename: Max
authors.initials: M
authors.lastname: Pillong
authors.forename: Renato B
authors.initials: RB
authors.lastname: Baleeiro
authors.forename: Michael
authors.initials: M
authors.lastname: Reutlinger
authors.forename: Gerd
authors.initials: G
authors.lastname: Folkers
authors.forename: Peter
authors.initials: P
authors.lastname: Walden
authors.forename: Paul
authors.initials: P
authors.lastname: Wrede
authors.forename: Jan A
authors.initials: JA
authors.lastname: Hiss
authors.forename: Zoe
authors.initials: Z
authors.lastname: Waibler
authors.forename: Gisbert
authors.initials: G
authors.lastname: Schneider
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001185:Artificial Intelligence; D005805:Genes, MHC Class I; D006183:H-2 Antigens / Q000276:immunology*; D053123:Influenza A Virus, H3N8 Subtype / Q000276:immunology*; D008024:Ligands; D051379:Mice; D009842:Oligopeptides / Q000737:chemistry / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000821:virology; D020543:Proteome / Q000276:immunology*; D018353:Rhabdoviridae Infections / Q000821:virology; D018116:Vesiculovirus / Q000276:immunology*
chemical_list: D006183:H-2 Antigens; D008024:Ligands; D009842:Oligopeptides; D020543:Proteome