Abstract
In vivo bioluminescence imaging of reporter enzymes has proven to be a uniquely powerful tool that allows the study of the biology of viral and nonviral gene transfer agents. Cost-effective, noninvasive, longitudinal gene transfer studies in individual animals yield important information, which can influence the design of subsequent preclinical studies. The broad and expanding use of luciferase transgenes, specifically firefly luciferase, has prompted the study of luciferase-specific T-cell activation following in vivo gene transfer. Herein, we report the mapping of the dominant T cell epitope in C57BL/6 mice (LMYRFEEEL) and the mapping of the dominant and minor T-cell epitopes in BALB/c mice (GFQSMYTFV and VPFHHGFGM, VALPHRTAC, respectively). These CD8 T-cell epitopes can be used to monitor cellular responses in vivo as well as be important tools in studies designed to suppress transgene-specific T cells.
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Acknowledgements
We thank Deirdre McMenamin and Regina Munden for invaluable assistance with animal studies; Roberto Calcedo for expert assistance with FACS analysis; Arbans Sandhu and Julie Johnston (Penn Vector) for supplying the Ad.Hu5 vectors. This work was supported by grants from the Cystic Fibrosis Foundation (R881), P01-HL051746 and GSK. JMW is an inventor on patents licensed to various commercial entities.
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Limberis, M., Bell, C. & Wilson, J. Identification of the murine firefly luciferase-specific CD8 T-cell epitopes. Gene Ther 16, 441–447 (2009). https://doi.org/10.1038/gt.2008.177
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DOI: https://doi.org/10.1038/gt.2008.177
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