Immunological validation of the EpitOptimizer program for streamlined design of heteroclitic epitopes Journal Article
| Authors: | Houghton, C. S. B.; Engelhorn, M. E.; Liu, C.; Song, D.; Gregor, P.; Livingston, P. O.; Orlandi, F.; Wolchok, J. D.; McCracken, J.; Houghton, A. N.; Guevara-Patiño, J. A. |
| Article 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. |
| Keywords: | controlled study; unclassified drug; nonhuman; validation process; neoplasms; t cells; cd8+ t lymphocyte; cd8-positive t-lymphocytes; animal cell; mouse; animals; mice; computational biology; animal experiment; drug design; algorithms; wild type; mice, inbred c57bl; mice, transgenic; models, animal; amino acid sequence; molecular sequence data; cancer vaccines; algorithm; cancer immunization; vaccination; epitope; tumor protein; histocompatibility antigens class i; peptides; tumor immunity; immunological adjuvant; mutagenesis, site-directed; computer program; major histocompatibility antigen class 1; plasmid dna; peptide derivative; epitopes; cross reactions; protein engineering; antigens/peptides/epitopes; titermax |
| Journal Title: | Vaccine |
| Volume: | 25 |
| Issue: | 29 |
| ISSN: | 0264-410X |
| Publisher: | Elsevier Inc. |
| Date Published: | 2007-07-20 |
| Start Page: | 5330 |
| End Page: | 5342 |
| Language: | English |
| DOI: | 10.1016/j.vaccine.2007.05.008 |
| PUBMED: | 17570567 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 11" - "Export Date: 17 November 2011" - "CODEN: VACCD" - "Source: Scopus" |
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