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Lee, S.P.* ; Brooks, J.M.* ; Al-Jarrah, H.* ; Thomas, W.A.* ; Haigh, T.A.* ; Taylor, G.S.* ; Humme, S. ; Schepers, A. ; Hammerschmidt, W. ; Yates, J.L.* ; Rickinson, A.B.*

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

J. Exp. Med. 199, 1409-1420 (2004)
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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 γ 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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Epstein-Barr virus; cytotoxic T lymphocytes; antigen presentation; EBNA1
ISSN (print) / ISBN 0022-1007
e-ISSN 1540-9538
Journal Journal of Experimental Medicine
Quellenangaben Volume: 199, Issue: 10, Pages: 1409-1420 Article Number: , Supplement: ,
Publisher Rockefeller University Press
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Research Unit Gene Vector (AGV)