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.
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.
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