title: Characterization of Immunodominant BK Polyomavirus 9mer Epitope T Cell Responses.
abstract: Uncontrolled BK polyomavirus (BKPyV) replication in kidney transplant recipients (KTRs) causes polyomavirus-associated nephropathy and allograft loss. Reducing immunosuppression is associated with clearing viremia and nephropathy and increasing BKPyV-specific T cell responses in most patients; however, current immunoassays have limited sensitivity, target mostly CD4(+) T cells, and largely fail to predict onset and clearance of BKPyV replication. To characterize BKPyV-specific CD8(+) T cells, bioinformatics were used to predict 9mer epitopes in the early viral gene region (EVGR) presented by 14 common HLAs in Europe and North America. Thirty-nine EVGR epitopes were experimentally confirmed by interferon-γ enzyme-linked immunospot assays in at least 30% of BKPyV IgG-seropositive healthy participants. Most 9mers clustered in domains, and some were presented by more than one HLA class I, as typically seen for immunodominant epitopes. Specific T cell binding using MHC class I streptamers was demonstrated for 21 of 39 (54%) epitopes. In a prospective cohort of 118 pediatric KTRs, 19 patients protected or recovering from BKPyV viremia were experimentally tested, and 13 epitopes were validated. Single HLA mismatches were not associated with viremia, suggesting that failing immune control likely involves multiple factors including maintenance immunosuppression. Combining BKPyV load and T cell assays using immunodominant epitopes may help in evaluating risk and reducing immunosuppression and may lead to safe adoptive T cell transfer.
authors.affiliation: Transplantation and Clinical Virology, Department Biomedicine (Haus Petersplatz), University of Basel, Basel, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Cioni
authors.affiliation: Transplantation and Clinical Virology, Department Biomedicine (Haus Petersplatz), University of Basel, Basel, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Leboeuf
authors.affiliation: Pediatric Hematology/Oncology, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Comoli
authors.affiliation: Nephrology, Dialysis and Transplantation Unit, IRCCS G. Gaslini Institute, Genova, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Ginevri
authors.affiliation: Transplantation and Clinical Virology, Department Biomedicine (Haus Petersplatz), University of Basel, Basel, Switzerland.|Division of Infection Diagnostics, Department Biomedicine (Haus Petersplatz), University of Basel, Basel, Switzerland.|Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland.
authors.forename: H H
authors.initials: HH
authors.lastname: Hirsch
mesh_terms: D001739:BK Virus / Q000276:immunology* / Q000502:physiology; D002648:Child; D058501:Enzyme-Linked Immunospot Assay; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000601:surgery / Q000821:virology; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D027601:Polyomavirus Infections / Q000175:diagnosis / Q000276:immunology*; D011446:Prospective Studies; D013601:T-Lymphocytes / Q000276:immunology*; D014412:Tumor Virus Infections / Q000175:diagnosis / Q000276:immunology*; D014779:Virus Replication
chemical_list: D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens