title: Definition and characterization of novel HLA-*A02-restricted CD8+ T cell epitopes derived from JCV polyomavirus with clinical relevance.
abstract: Human JC and BK polyomaviruses (JCV/BKV) can establish a latent infection without any clinical symptoms in healthy individuals. In immunocompromised hosts infection or reactivation of JCV and BKV can cause lethal progressive multifocal leukoencephalopathy (PML) and hemorrhagic cystitis, respectively. Vaccination with JCV/BKV derived antigen epitope peptides or adoptive transfer of virus-specific T cells would constitute an elegant approach to clear virus-infected cells. Furthermore, donor leukocyte infusion (DLI) is another therapeutic approach which could be helpful for patients with JCV/BKV infections.So far, only few immunodominant T cell epitopes of JCV and BKV have been described and therefore is a fervent need for the definition of novel epitopes. In this study, we identified novel T cell epitopes by screening libraries of overlapping peptides derived from the major capsid protein VP1 of JCV. Virus like particles (VLPs) were used to confirm naturally processing. Two human leucocyte antigen (HLA)-A*02-restricted epitopes were characterized by fine mapping with overlapping peptides and nonamer peptide sequences were identified. Cytokine release profile of the epitope-specific T cells was analyzed by enzyme-linked immunospot (ELISPOT) assays and by flow cytometry. We demonstrated that T cell responses were of polyfunctional nature with the potential of epitope-specific killing and cross-reactivity between JCV and BKV. These novel epitopes might constitute a new potential tool to design effective diagnostic and therapeutic approaches against both polyomaviruses.
authors.affiliation: Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Jiju
authors.initials: J
authors.lastname: Mani
authors.affiliation: Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Angela G
authors.initials: AG
authors.lastname: Hückelhoven
authors.affiliation: Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Anita
authors.initials: A
authors.lastname: Schmitt
authors.affiliation: Department of Eukaryote Genetic Engineering, Institute of Biotechnology, Vilnius University, Vilnius, Lithuania.
authors.forename: Alma
authors.initials: A
authors.lastname: Gedvilaite
authors.affiliation: Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany.|Department of Hematology, ZhongDa Hospital, Southeast University, Nanjing, P. R. China.
authors.forename: Nan
authors.initials: N
authors.lastname: Jin
authors.affiliation: Department of Transplantation Immunology, Heidelberg University Hospital, Heidelberg, Germany.|Department of Nuclear Medicine, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Kleist
authors.affiliation: Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Ho
authors.affiliation: Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schmitt
mesh_terms: D000595:Amino Acid Sequence; D001739:BK Virus / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003429:Cross Reactions; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism*; D015789:HLA-A2 Antigen / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007577:JC Virus / Q000276:immunology*; D015678:Viral Structural Proteins / Q000276:immunology
chemical_list: D018984:Epitopes, T-Lymphocyte; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D015678:Viral Structural Proteins
keywords: JCV; T cell epitopes; immunotherapy; progressive multifocal leukoencephalopathy; virus like particles