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Journal of Virology, January 2008, p. 546-554, Vol. 82, No. 1
0022-538X/08/$08.00+0     doi:10.1128/JVI.01689-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Identification of Hexon-Specific CD4 and CD8 T-Cell Epitopes for Vaccine and Immunotherapy{triangledown}

Ann M. Leen,1,2* Anne Christin,1,2 Mariam Khalil,1,2 Heidi Weiss,4 Adrian P. Gee,1,2,4 Malcolm K. Brenner,1,2,4 Helen E. Heslop,1,2,4 Cliona M. Rooney,1,2,3,5 and Catherine M. Bollard1,2,3,4

Center for Cell and Gene Therapy,1 Departments of Pediatrics,2 Immunology,3 Medicine,4 Virology, Baylor College of Medicine, the Methodist Hospital and Texas Children's Hospital, Houston, Texas 770305

Received 3 August 2007/ Accepted 9 October 2007

Adenoviral infections in the immunocompromised host are associated with significant morbidity and mortality. Although the adoptive transfer of adenovirus-specific T cells may prevent and treat such infections, the T-cell immune response to the multiplicity of adenovirus serotypes and subspecies that infect humans has not been well characterized, impeding the development of such approaches. We have, therefore, analyzed the specificities of T-cell responses to the viral capsid hexon antigen, since this structure is highly conserved in human pathogens. We screened 25 human cytotoxic T-cell lines with adenovirus specificity to extensively characterize their responses to adenoviral hexon and to identify a panel of novel CD4+ and CD8+ T-cell epitopes. Using a peptide library spanning the entire sequence of the hexon protein, we confirmed the responsiveness of these cytotoxic T-cell lines to seven peptides described previously and also identified 33 new CD4- or CD8-restricted hexon epitopes. Importantly, the majority of these epitopes were shared among different adenovirus subspecies, suggesting that T cells with such specificities could recognize and be protective against multiple serotypes, simplifying the task of effective adoptive transfer or vaccine-based immunotherapy for treating infection by this virus.


* Corresponding author. Mailing address: Center for Cell and Gene Therapy, Baylor College of Medicine, 6621 Fannin Street, MC 3-3320, Houston, TX 77030. Phone: (832) 824-4690. Fax: (832) 825-4732. E-mail: amleen{at}txccc.org

{triangledown} Published ahead of print on 17 October 2007.


Journal of Virology, January 2008, p. 546-554, Vol. 82, No. 1
0022-538X/08/$08.00+0     doi:10.1128/JVI.01689-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.




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