Conserved CTL epitopes on the adenovirus hexon protein expand subgroup cross-reactive and subgroup-specific CD8+ T cells.
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.
Leen
Ann M
AM
Center for Cell and Gene Therapy, Department of Pediatrics, 6621 Fannin St, MC 3-3320, Houston, TX, USA.
Sili
Uluhan
U
Vanin
Elio F
EF
Jewell
Alan M
AM
Xie
Weidong
W
Vignali
Dario
D
Piedra
Pedro A
PA
Brenner
Malcolm K
MK
Rooney
Cliona M
CM
D000256:Adenoviridae / Q000276:immunology*; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D036022:Capsid Proteins / Q000737:chemistry / Q000276:immunology*; D002478:Cells, Cultured; D017124:Conserved Sequence; D003429:Cross Reactions / Q000276:immunology*; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D015234:HLA-A Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D036022:Capsid Proteins; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; D010455:Peptides; C018315:hexon capsid protein, Adenovirus