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| Item Type: | Article |
|---|---|
| Title: | Codon optimization of the human papillomavirus E7 oncogene induces a CD8(+) T cell response to a cryptic epitope not harbored by wild-type E7 |
| Creators Name: | Lorenz, F.K.M., Wilde, S., Voigt, K., Kieback, E., Mosetter, B., Schendel, D.J. and Uckert, W. |
| Abstract: | Codon optimization of nucleotide sequences is a widely used method to achieve high levels of transgene expression for basic and clinical research. Until now, immunological side effects have not been described. To trigger T cell responses against human papillomavirus, we incubated T cells with dendritic cells that were pulsed with RNA encoding the codon-optimized E7 oncogene. All T cell receptors isolated from responding T cell clones recognized target cells expressing the codon-optimized E7 gene but not the wild type E7 sequence. Epitope mapping revealed recognition of a cryptic epitope from the +3 alternative reading frame of codon-optimized E7, which is not encoded by the wild type E7 sequence. The introduction of a stop codon into the +3 alternative reading frame protected the transgene product from recognition by T cell receptor gene-modified T cells. This is the first experimental study demonstrating that codon optimization can render a transgene artificially immunogenic through generation of a dominant cryptic epitope. This finding may be of great importance for the clinical field of gene therapy to avoid rejection of gene-corrected cells and for the design of DNA- and RNA-based vaccines, where codon optimization may artificially add a strong immunogenic component to the vaccine. |
| Keywords: | CD8-Positive T-Lymphocytes, Codon, Cultured Cells, Epitope Mapping, Genetic Therapy, Papillomaviridae, Papillomavirus E7 Proteins |
| Source: | PLoS ONE |
| ISSN: | 1932-6203 |
| Publisher: | Public Library of Science |
| Volume: | 10 |
| Number: | 3 |
| Page Range: | e0121633 |
| Date: | 23 March 2015 |
| Official Publication: | https://doi.org/10.1371/journal.pone.0121633 |
| PubMed: | View item in PubMed |
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