Abstract
When using adenovirus as a vector for the delivery of transgenes, the induction of a cytotoxic T lymphocytes (CTL) can limit the longevity of the transgene expression (1,2). To detect the CTL response to adenovirus proteins or inserted transgenes in a mouse model, even with multiple in vivo immunizations, a secondary in vitro restimulation is necessary. The CTL response to adenovirus tends to focus on one or a few immunodominant epitopes. Using secondary in vitro restimulation of spleen cells from primed mice as described here, an adenovirus-specific, MHC class I-restricted CTL response has been generated that recognizes different immunodominant adenovirus antigens depending on the haplotype of the mice (3,4). Using various adenovirus deletion mutants or transfectants expressing individual adenovirus proteins, it is possible to map the CTL antigens. With this knowledge, it is possible to investigate methods for reducing or limiting the CTL response.
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References
Yang, Y., Li, Q., Ertl, H C., and Wilson, J. M. (1995) Cellular and humoral immune responses to viral antigens create barriers to lung-directed gene therapy with recombinant adenoviruses. J Virol 69, 2004–2015
Yang, Y., Nunes, F A., Berencsi, K., Furth, E E., Gonczol, E., and Wilson, J. M. (1994) Cellular immunity to viral antigens limits E1-deleted adenoviruses for gene therapy. Proc Natl Acad Sci USA 91, 4407–4411.
Rawle, F., Knowles, B. B., Ricciardi, R P., Brahmacheri, V., Duerksen-Hughes, P., Wold, W. S M., and Gooding, L. R. (1991) Specificity of the mouse cytotoxic T lymphocyte response to Adenovirus 5 Immunodominance of E1A depends on H-2 haplotype. J Immunol. 146, 3977–3984
Sparer, T., Wynn, S. G., Clark, D J., Kaplan, J. M., Cardoza, L. M., Wadsworth, S. C., Smith, A E., and Gooding, L R. (1997) Generation of cytotoxic T lymphocytes against immunorecessive epitopes after multiple immunizations with adenovirus vectors is dependent on haplotype. J Virol 71, 2277–2284.
Wold, W S. M and Gooding, L. R. (1991) Region E3 of adenovirus$$ a cassette of genes involved in host immunosurveillance and virus-cell interactions Virology 184, 1–8
Rawle, F. C., Tollefson, A. E., Wold, W. S. M., and Gooding, L R (1989) Mouse anti-adenovirus CTL. Inhibition of lysis by E3 gp19K but not E3 14.7K. J immunol 143, 2031–2037.
Sparer, T., Tripp, R. A., Dillehay, D. L., Hermiston, T W., Wold, W S M., and Gooding, L R. (1996) The role of adenovirus early region 3 proteins (19K, 10 4K, 14.5K, and 14.7K) in a murine pneumonia model J Virol. 70, 2431–2439
Gooding, L. R. (1979) Specificities of killing by T lymphocytes generated against syngeneic SV40 transformants. Studies employing recombinants within the H-2 complex. J. Immunol 122, 1002–1008.
Gooding, L R (1977) Specificities of killing by cytotoxic T lymphocytes generated in vivo and in vitro to syngeneic SV40 transformed cells. J Immunol 118, 920–927
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© 1999 Humana Press Inc., Totowa, NJ
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Sparer, T.E., Gooding, L.R. (1999). Generation of Adenovirus-Specific Cytotoxic T Lymphocytes. In: Wold, W.S.M. (eds) Adenovirus Methods and Protocols. Methods in Molecular Medicine™, vol 21. Springer, Totowa, NJ. https://doi.org/10.1385/0-89603-551-4:105
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DOI: https://doi.org/10.1385/0-89603-551-4:105
Publisher Name: Springer, Totowa, NJ
Print ISBN: 978-0-89603-551-5
Online ISBN: 978-1-59259-603-4
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