Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10970536 | Vaccine | 2007 | 13 Pages |
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.
Keywords
Related Topics
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Immunology
Authors
Colin S.B. Houghton, Manuel E. Engelhorn, Cailan Liu, Da Song, Polly Gregor, Phillip O. Livingston, Francesca Orlandi, Jedd D. Wolchok, James McCracken, Alan N. Houghton, José A. Guevara-Patiño,