BK-VP3 as a new target of cellular immunity in BK virus infection

Transplantation. 2011 Jan 15;91(1):100-7. doi: 10.1097/tp.0b013e3181fe1335.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, Viral / immunology
  • BK Virus / immunology*
  • Creatinine / blood
  • Female
  • Flow Cytometry
  • Humans
  • Immunity, Cellular / immunology*
  • Interferon-gamma / immunology
  • Interleukin-2 / immunology
  • Kidney Transplantation / immunology
  • Male
  • Middle Aged
  • Polyomavirus Infections / immunology*
  • Retrospective Studies
  • T-Lymphocytes / immunology*
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Virus Infections / immunology*
  • Viral Core Proteins / immunology*


  • Antigens, Viral
  • Interleukin-2
  • Tumor Necrosis Factor-alpha
  • Viral Core Proteins
  • Interferon-gamma
  • Creatinine