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Blood, 15 October 2004, Vol. 104, No. 8, pp. 2432-2440.
Prepublished online as a Blood First Edition Paper on July 20, 2004; DOI 10.1182/blood-2004-02-0646.


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IMMUNOBIOLOGY

Conserved CTL epitopes on the adenovirus hexon protein expand subgroup cross-reactive and subgroup-specific CD8+ T cells

Ann M. Leen, Uluhan Sili, Elio F. Vanin, Alan M. Jewell, Weidong Xie, Dario Vignali, Pedro A. Piedra, Malcolm K. Brenner, and Cliona M. Rooney

From the Center for Cell and Gene Therapy, the Department of Pediatrics, the Department of Medicine, and the Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX; the Methodist Hospital and Texas Children's Hospital, Houston, TX; and the Department of Immunology, St Jude Children's Hospital, Memphis, TN.

Adenoviruses often cause lethal infections in immunocompromised individuals. Adoptive transfer of immune T cells offers a therapeutic option, but this strategy has been hindered by the paucity of information on molecular targets of cellular immunity and by the immunologic heterogeneity of the 51 human adenoviruses, which are grouped from A to F on the basis of genome size, composition, homology, and organization. Clonal analysis of the adenovirus-specific cytotoxic T lymphocyte (CTL) responses of seropositive individuals identified 5 novel CD8+ T-cell epitopes, all located in conserved regions of the capsid protein hexon. Reactive T cells were cross-reactive between 2 to 4 groups, while no T cells specific for a single subgroup were detected. Thus, by exploiting these peptide targets, it is possible to prepare a T-cell population capable of reacting with most adenoviruses that cause disease in immunocompromised patients.


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