title: Immunological validation of the EpitOptimizer program for streamlined design of heteroclitic epitopes.
abstract: One strategy to generate T-cell responses to tumors is to alter subdominant epitopes through substitution of amino acids that are optimal anchors for specific MHC molecules, termed heteroclitic epitopes. This approach is manually error-prone and time-consuming. In here, we describe a computer-based algorithm (EpitOptimizer) for the streamlined design of heteroclitic epitopes. Analysis of two cancer-related proteins showed that EpitOptimizer-generated peptides have enhanced MHC-I binding compared with their wild-type counterparts; and were able to induce stronger CD8+ T-cell responses against their native epitope. These data demonstrate that this approach can serve as the basis of epitope-engineering against cancer and intracellular pathogens.
authors.affiliation: The Swim Across America Laboratory, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, United States.
authors.forename: Colin S B
authors.initials: CS
authors.lastname: Houghton
authors.forename: Manuel E
authors.initials: ME
authors.lastname: Engelhorn
authors.forename: Cailan
authors.initials: C
authors.lastname: Liu
authors.forename: Da
authors.initials: D
authors.lastname: Song
authors.forename: Polly
authors.initials: P
authors.lastname: Gregor
authors.forename: Phillip O
authors.initials: PO
authors.lastname: Livingston
authors.forename: Francesca
authors.initials: F
authors.lastname: Orlandi
authors.forename: Jedd D
authors.initials: JD
authors.lastname: Wolchok
authors.forename: James
authors.initials: J
authors.lastname: McCracken
authors.forename: Alan N
authors.initials: AN
authors.lastname: Houghton
authors.forename: José A
authors.initials: JA
authors.lastname: Guevara-Patiño
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D019295:Computational Biology / Q000379:methods*; D003429:Cross Reactions; D000939:Epitopes / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D023421:Models, Animal; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009369:Neoplasms; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015202:Protein Engineering
chemical_list: D019496:Cancer Vaccines; D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D010455:Peptides