title: Novel pan-DR-binding T cell epitopes of adenovirus induce pro-inflammatory cytokines and chemokines in healthy donors.
abstract: Adenovirus can cause fatal infections in the immunocompromised host. To date, no effective anti-viral therapy is available. Adoptive therapy with adenovirus-specific T cells could be a promising treatment, but requires the identification of such T cells. Aim of this study was to identify conserved adenoviral T cell epitopes recognized in a majority of healthy individuals. By using a computer algorithm designed to predict pan-HLA-DR-binding T cell epitopes, we selected 19 peptides of adenovirus serotype 5. PBMCs from 26 healthy subjects were isolated and incubated with these peptides to test epitope-specific T cell proliferation. Six epitopes derived from E1B protein, hexon protein (two epitopes), DNA polymerase, E3A glycoprotein and fiber protein induced a proliferative T cell response in the majority of healthy controls. In vitro MHC binding assays confirmed the potential capacity of the adenovirus epitopes to bind multiple MHC alleles. The cytokine and chemokine profile induced by these epitopes was determined with a multiplex immunoassay and revealed a predominant pro-inflammatory pattern. Based on the broad recognition and the induced cytokine and chemokine profile, the detected epitopes can be regarded as potential candidates to select adenovirus-specific T cells for immune intervention in the immunocompromised host.
authors.affiliation: Department of Pediatric Immunology and Hematology, Wilhelmina Children's Hospital, University Medical Center, KC.03.063.0, Lundlaan 6, Postbus 85090, 3508 AB, Utrecht, The Netherlands.
authors.forename: Lianne M
authors.initials: LM
authors.lastname: Haveman
authors.forename: Marc
authors.initials: M
authors.lastname: Bierings
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Legger
authors.forename: Mark R
authors.initials: MR
authors.lastname: Klein
authors.forename: Wilco
authors.initials: W
authors.lastname: de Jager
authors.forename: Henny G
authors.initials: HG
authors.lastname: Otten
authors.forename: Salvatore
authors.initials: S
authors.lastname: Albani
authors.forename: Wietse
authors.initials: W
authors.lastname: Kuis
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sette
authors.forename: Berent J
authors.initials: BJ
authors.lastname: Prakken
mesh_terms: D000256:Adenoviridae / Q000276:immunology*; D000465:Algorithms; D000595:Amino Acid Sequence; D049109:Cell Proliferation; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006684:HLA-DR Antigens; D006801:Humans; D007118:Immunoassay; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
chemical_list: D018925:Chemokines; D016207:Cytokines; D004268:DNA-Binding Proteins; D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens