title: Identification of a novel HLA-A*24:02-restricted adenovirus serotype 11-specific CD8+ T-cell epitope for adoptive immunotherapy.
abstract: Subgroup B adenovirus serotype 11 (Ad11) occasionally causes fatal infections in immunocompromised patients. The present study describes a novel Ad11 epitope presented by HLA-A*24:02 that could be used for adoptive immunotherapy. Ten synthetic Ad11 hexon protein-derived nonamer peptides that bound to HLA-A*24:02 were selected by a computer algorithm and MHC stabilization assay. Stimulation of peripheral blood mononuclear cells from HLA-A*24:02+ donors with each of these synthetic peptides induced peptide-specific CD8(+) T-cells for three peptides. Testing the reactivity of these peptide-specific CD8(+) T-cells against various target cells confirmed that peptide TYFNLGNKF is naturally processed in Ad11-infected cells and is presented by HLA-A*24:02. Emergence of TYFNLGNKF-specific CD8(+) T-cells coincided with the clearance of adenoviruses in a patient with Ad11 disease. Importantly, TYFNLGNKF-specific CD8(+) T-cells were suggested to be not serotype cross-reactive. The novel HLA-A*24:02-restricted Ad11 epitope could be used for anti-Ad11 adoptive immunotherapy and to monitor immunity to Ad11 using MHC tetramers.
authors.affiliation: Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan; Research Fellow of Japan Society for the Promotion of Science, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Imahashi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nishida
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ito
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Kawada
authors.forename: Yozo
authors.initials: Y
authors.lastname: Nakazawa
authors.forename: Shingo
authors.initials: S
authors.lastname: Toji
authors.forename: Susumu
authors.initials: S
authors.lastname: Suzuki
authors.forename: Seitaro
authors.initials: S
authors.lastname: Terakura
authors.forename: Tomonori
authors.initials: T
authors.lastname: Kato
authors.forename: Makoto
authors.initials: M
authors.lastname: Murata
authors.forename: Tomoki
authors.initials: T
authors.lastname: Naoe
mesh_terms: D000256:Adenoviridae / Q000145:classification / Q000235:genetics / Q000276:immunology*; D000595:Amino Acid Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D059871:HLA-A24 Antigen / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D020014:K562 Cells; D011485:Protein Binding / Q000276:immunology; D012703:Serotyping
chemical_list: D018984:Epitopes, T-Lymphocyte; C438506:HLA-A*24:02 antigen; D059871:HLA-A24 Antigen
keywords: Ad11; AdV; Adenovirus; Adoptive therapy; BIMAS; Bioinformatics and Molecular Analysis Section; CM; CMV; CTLs; Cytotoxic T-cells; E:T; EBV; ELISA; Epitope; Epstein-Barr virus; Epstein-Barr virus-transformed B-lymphoblastoid cell lines; FBS; HC; HSCT; IFN-γ; IL-2; K562 cells transduced with HLA-A*24:02; K562/A*24:02; LCLs; LYA; LYANSAHAL; MFI; PBMCs; T cell receptors; TCRs; TYF; TYFNLGNKF; VYS; VYSGSIPYL; adenovirus serotype 11; adenoviruses; culture medium; cytomegalovirus; cytotoxic T-cells; effector to target; enzyme-linked immunosorbent assay; fetal bovine serum; hematopoietic stem cell transplantation; hemorrhagic cystitis; interferon-γ; interleukin-2; mAb; mean fluorescence intensity; monoclonal antibody; peripheral blood mononuclear cells