Definition and characterization of novel HLA-*A02-restricted CD8 + T cell epitopes derived from JCV polyomavirus with clinical relevance

// Jiju Mani 1 , Lei Wang 1 , Angela G. Huckelhoven 1 , Anita Schmitt 1 , Alma Gedvilaite 2 , Nan Jin 1, 3 , Christian Kleist 4, 5 , Anthony D. Ho 1 , Michael Schmitt 1 1 Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany 2 Department of Eukaryote Genetic Engineering, Institute of Biotechnology, Vilnius University, Vilnius, Lithuania 3 Department of Hematology, ZhongDa Hospital, Southeast University, Nanjing, P. R. China 4 Department of Transplantation Immunology, Heidelberg University Hospital, Heidelberg, Germany 5 Department of Nuclear Medicine, Heidelberg University Hospital, Heidelberg, Germany Correspondence to: Michael Schmitt, email: Michael.schmitt@med.uni-heidelberg.de Keywords: JCV, T cell epitopes, progressive multifocal leukoencephalopathy, virus like particles, immunotherapy Received: June 29, 2016     Accepted: September 19, 2016     Published: October 01, 2016 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.