title: BK-VP3 as a new target of cellular immunity in BK virus infection.
abstract: BACKGROUND
  Polyomavirus BK virus (BKV) infection represents a serious complication leading to BKV-associated nephropathy (BKVAN) and subsequent kidney graft loss in up to 10% of transplant patients. Cellular immunity is known to play a crucial role in the control of BKV replication. However, the knowledge on the BKV-T-cell response is limited: only two (VP1 and large T antigen) of six known BKV proteins were evaluated for their antigenicity so far.
  
  
  METHODS
  By using 10-color flow cytometry and newly created overlapping peptide pools of five BKV antigens (VP1, VP2, VP3, large T antigen, and small t antigen), we performed cross-sectional phenotypic and functional analysis of BKV-specific T cells in kidney transplant patients with a history of BKVAN. Patients with clinically unapparent BKV infection (history of transient/no BKV reactivation) were used as control group.
  
  
  RESULTS
  Our data demonstrate for the first time the antigenic properties of all five evaluated proteins with VP3 as a new important target of cellular immunity. Further, we found a correlation between the severity of the previous BKV infection and the magnitude of memory CD4+ T-cell response. Thus, compared with the control group, patients with a history of BKVAN demonstrated significantly higher frequencies of interferon-γ- and interleukin-2-producing effector memory CD4+ T cells. In the control group, more patients with detectable interferon-γ+/interleukin-2+/tumor necrosis factor+ triple producers were found, suggesting possibly a protective function of these multifunctional T cells.
  
  
  CONCLUSIONS
  In conclusion, our study results suggest an implementation of new targets for monitoring of BKV immunity. Further studies are required to evaluate the protective function of the found BKV-specific T-cell subsets.
authors: Department of Nephrology, Charite University Medicine Berlin, Campus Virchow Clinic, Berlin, Germany.
authors: Karin
authors: K
authors: Mueller
authors: Thomas
authors: T
authors: Schachtner
authors: Arne
authors: A
authors: Sattler
authors: Sarah
authors: S
authors: Meier
authors: Peter
authors: P
authors: Friedrich
authors: Hanna
authors: H
authors: Trydzenskaya
authors: Carl
authors: C
authors: Hinrichs
authors: Ralf
authors: R
authors: Trappe
authors: Andreas
authors: A
authors: Thiel
authors: Petra
authors: P
authors: Reinke
authors: Nina
authors: N
authors: Babel
mesh_terms: D000328:Adult; D000368:Aged; D000956:Antigens, Viral / Q000276:immunology; D001739:BK Virus / Q000276:immunology*; D003404:Creatinine / Q000097:blood; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D016030:Kidney Transplantation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D027601:Polyomavirus Infections / Q000276:immunology*; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014412:Tumor Virus Infections / Q000276:immunology*; D014758:Viral Core Proteins / Q000276:immunology*
chemical_list: D000956:Antigens, Viral; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D014758:Viral Core Proteins; D007371:Interferon-gamma; D003404:Creatinine