title: Human CD4+ T cells stimulated by conserved adenovirus 5 hexon peptides recognize cells infected with different species of human adenovirus.
abstract: The immune response against human adenovirus (HAdV) has gained interest because of the application of HAdV-based vectors in gene therapy and the high incidence of infections in pediatric recipients of allogeneic stem cell grafts. Because antiviral medication is frequently ineffective, the option of adoptive transfer of HAdV-specific donor-derived T cells in these immunocompromised patients is investigated. To generate good manufacturing practice-compatible reagents, a panel of 63 long, overlapping, peptides of the hexon protein was screened for recognition by T cells. Five conserved peptides of 30 amino acids were identified that were recognized by the majority of adult donors. CD4+ T cells from long-term cultures of PBMC, stimulated with this set of five peptides, recognized cells infected with HAdV serotypes belonging to different species. These data demonstrate that adult human T cells preferentially recognize conserved sequences of amino acid residues from a structural protein of HAdV. In the context of gene therapy, this observation may limit the beneficial effect of switching to HAdV-based vectors derived from less common serotypes of HAdV in an attempt to circumvent pre-existing immunity. However, this cross-reactivity benefits the application of HAdV-specific T cells for adoptive immunotherapy in immunocompromised transplant recipients.
authors.affiliation: Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Louise A
authors.initials: LA
authors.lastname: Veltrop-Duits
authors.forename: Bianca
authors.initials: B
authors.lastname: Heemskerk
authors.forename: Claudia C
authors.initials: CC
authors.lastname: Sombroek
authors.forename: Tamara
authors.initials: T
authors.lastname: van Vreeswijk
authors.forename: Sophie
authors.initials: S
authors.lastname: Gubbels
authors.forename: René E M
authors.initials: RE
authors.lastname: Toes
authors.forename: Cornelis J M
authors.initials: CJ
authors.lastname: Melief
authors.forename: Kees L M C
authors.initials: KL
authors.lastname: Franken
authors.forename: Menzo
authors.initials: M
authors.lastname: Havenga
authors.forename: Maarten J D
authors.initials: MJ
authors.lastname: van Tol
authors.forename: Marco W
authors.initials: MW
authors.lastname: Schilham
mesh_terms: D000260:Adenoviruses, Human / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology*; D017124:Conserved Sequence / Q000276:immunology*; D003429:Cross Reactions; D006801:Humans; D016133:Polymerase Chain Reaction
chemical_list: D036022:Capsid Proteins; C018315:hexon capsid protein, Adenovirus