T cells specific for different latent and lytic viral proteins efficiently control Epstein-Barr virus-transformed B cells

Justyna Nowakowska, Claudia Stuehler, Adrian Egli, Manuel Battegay, Georg Rauser, Glenn Robert Bantug, Christian Brander, Christoph Hess, Nina Khanna

Research output: Contribution to journalArticleResearchpeer-review

6 Citations (Scopus)


© 2015 International Society for Cellular Therapy. Background aims: Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disorders (PTLD) belong to the most dreaded complications of immunosuppression. The efficacy of EBV-specific T-cell transfer for PTLD has been previously shown, yet the optimal choice of EBV-derived antigens inducing polyclonal CD4+ and CD8+ T cells that cover a wide range of human leukocyte antigen types and efficiently control PTLD remains unclear. Methods: A pool of 125 T-cell epitopes from seven latent and nine lytic EBV-derived proteins (EBVmix) and peptide pools of EBNA1, EBNA3c, LMP2a and BZLF1 were used to determine T-cell frequencies and to isolate T cells through the use of the interferon (IFN)-γ cytokine capture system. We further evaluated the phenotype and functionality of the generated T-cell lines in vitro. Results: EBVmix induced significantly higher T-cell frequencies and allowed selecting more CD4+IFN-γ+ and CD8+IFN-γ+ cells than single peptide pools. T cells of all specificities expanded similarly in vitro, recognized cognate antigen, and, to a lower extent, EBV-infected cells, exerted moderate cytotoxicity and showed reduced alloreactivity. However, EBVmix-specific cells most efficiently controlled EBV-infected lymphoblastoid cell lines (LCLs). This control was mainly mediated by EBV-specific CD8+ cells with an oligoclonal epitope signature covering both latent and lytic viral proteins. Notably, EBV-specific CD4+ cells unable to control LCLs produced significantly less perforin and granzyme B, probably because of limited LCL epitope presentation. Conclusions: EBVmix induces a broader T-cell response, probably because of its coverage of latent and lytic EBV-derived proteins that may be important to control EBV-transformed B cells and might offer an improvement of T-cell therapies.
Original languageEnglish
Pages (from-to)1280-1291
Issue number9
Publication statusPublished - 1 Jan 2015


  • Epstein-Barr virus
  • IFN-γ selection
  • Immunotherapy
  • PTLD
  • T-cell transfer


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