title: Discovery of immunodominant T-cell epitopes reveals penton protein as a second immunodominant target in human adenovirus infection.
abstract: Human adenovirus (HAdV) infections remain a significant cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Efficient antiviral T-cell responses are necessary to clear infection, which is hampered by delayed immune reconstitution and medical immunosuppression after HSCT. Protective immunity may be conferred by adoptive transfer of HAdV-specific T cells. For identification of patients at risk and monitoring of treatment responses diligent assessment of anti-HAdV cellular immune responses is crucial. The HAdV-derived protein hexon has been recognized as a major immunodominant target across HAdV species. We aimed at identifying further targets of protective anti-HAdV immune response and characterizing immunogenic epitopes.
  
  
  
  Nineteen candidate nonamers from hexon and penton proteins were identified by epitope binding prediction. Peptides were synthesized and tested for in vivo immunogenicity by screening peripheral blood mononuclear cells from healthy volunteers (n = 64) and HAdV-infected stem cell recipients (n = 26) for memory T cells recognizing the candidate epitopes in the context of most common HLA alleles.
  
  
  
  Functional CD8+T cells recognizing seven epitopes were identified, among them four penton-derived and two hexon-derived peptides. The HLA-A*01-restricted penton-derived peptide STDVASLNY (A01PentonSTDV) and HLA-A*02-restricted hexon-derived peptide TLLYVLFEV (A02HexonTLLY) were recognized by more than half of the persons carrying the respective HLA-type.
  
  
  
  Thus, the HAdV-derived penton protein is a novel major target of the anti-HAdV immune response. Identification of new immunodominant epitopes will facilitate and broaden immune assessment strategies to identify patients suitable for T-cell transfer. Knowledge of additional target structures may increase T-cell recovery in manufacturing processes.
authors.affiliation: Institute for Transfusion Medicine, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany.|Integrated Research and Treatment Center (IFB-Tx), Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Tischer
authors.affiliation: St. Anna Kinderkrebsforschung e.V., Children's Cancer Research Institute, Vienna, Austria.
authors.forename: René
authors.initials: R
authors.lastname: Geyeregger
authors.affiliation: Institute for Transfusion Medicine, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany.
authors.forename: Julian
authors.initials: J
authors.lastname: Kwoczek
authors.affiliation: Institute for Virology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany.
authors.forename: Albert
authors.initials: A
authors.lastname: Heim
authors.affiliation: Institute for Transfusion Medicine, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany.
authors.forename: Constanca
authors.initials: C
authors.lastname: Figueiredo
authors.affiliation: Institute for Transfusion Medicine, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany.|Integrated Research and Treatment Center (IFB-Tx), Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Blasczyk
authors.affiliation: Integrated Research and Treatment Center (IFB-Tx), Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany.|Department of Paediatric Haematology and Oncology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Maecker-Kolhoff
authors.affiliation: Institute for Transfusion Medicine, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany. eiz-vesper.britta@mh-hannover.de.|Integrated Research and Treatment Center (IFB-Tx), Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany. eiz-vesper.britta@mh-hannover.de.
authors.forename: Britta
authors.initials: B
authors.lastname: Eiz-Vesper
mesh_terms: D000258:Adenovirus Infections, Human / Q000276:immunology*; D000260:Adenoviruses, Human / Q000276:immunology*; D000595:Amino Acid Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D036022:Capsid Proteins / Q000737:chemistry / Q000276:immunology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D005091:Exons / Q000235:genetics; D006680:HLA Antigens / Q000378:metabolism; D006801:Humans; D016056:Immunodominant Epitopes / Q000737:chemistry / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D018655:Lymphocyte Count; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D010641:Phenotype; D015203:Reproducibility of Results; D014019:Tissue Donors
chemical_list: D036022:Capsid Proteins; D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens; D016056:Immunodominant Epitopes; D010455:Peptides; C018315:hexon capsid protein, Adenovirus; C043322:penton protein, adenovirus; D007371:Interferon-gamma
keywords: Human adenovirus; Immunotherapy; Penton; T-cell epitope; T-cell monitoring