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Codon optimization of the human papillomavirus E7 oncogene induces a CD8(+) T cell response to a cryptic epitope not harbored by wild-type E7

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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. and Wilde, S. and Voigt, K. and Kieback, E. and Mosetter, B. and 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 (U.S.A.)
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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