CD8 T cell recognition of endogenously expressed Epstein-Barr virus nuclear antigen 1

Steven Lee, Jill Brooks, H Al-Jarrah, Wendy Thomas, Tracey Haigh, Graham Taylor, S Humme, A Schepers, W Hammerschmidt, JL Yates, Alan Rickinson, NW Blake

Research output: Contribution to journalArticle

131 Citations (Scopus)


The Epstein-Barr virus (EBV) nuclear antigen (EBNA)1 contains a glycine-alanine repeat (GAr) domain that appears to protect the antigen from proteasomal breakdown and, as measured in cytotoxicity assays, from major histocompatibility complex (MHC) class I-restricted presentation to CD8+ T cells. This led to the concept of EBNA1 as an immunologically silent protein that although unique in being expressed in all EBV malignancies, could not be exploited as a CD8 target. Here, using CD8+ T cell clones to native EBNA1 epitopes upstream and downstream of the GAr domain and assaying recognition by interferon gamma release, we show that the EBNA1 naturally expressed in EBV-transformed lymphoblastoid cell lines (LCLs) is in fact presented to CD8+ T cells via a proteasome/peptide transporter-dependent pathway. Furthermore, LCL recognition by such CD8+ T cells, although slightly lower than seen with paired lines expressing a GAr-deleted EBNA1 protein, leads to strong and specific inhibition of LCL outgrowth in vitro. Endogenously expressed EBNA1 is therefore accessible to the MHC class I pathway despite GAr-mediated stabilization of the mature protein. We infer that EBNA1-specific CD8+ T cells do play a role in control of EBV infection in vivo and might be exploitable in the control of EBV+ malignancies.
Original languageEnglish
Pages (from-to)1409-1420
Number of pages12
JournalThe Journal of Experimental Medicine
Publication statusPublished - 1 Jan 2004


  • cytotoxic T lymphocytes
  • Epstein-Barr virus
  • antigen presentation
  • EBNA1


Dive into the research topics of 'CD8 T cell recognition of endogenously expressed Epstein-Barr virus nuclear antigen 1'. Together they form a unique fingerprint.

Cite this