Direct killing of Epstein-Barr virus (EBV)-infected B cells by CD4 T cells directed against the EBV lytic protein BHRF1

Elise Landais, Xavier Saulquin, Emmanuel Scotet, Lydie Trautmann, Marie Alix Peyrat, John L. Yates, William W. Kwok, Marc Bonneville, Elisabeth Houssaint

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

Due to their low frequency, CD4 T-cell responses to Epstein-Barr virus (EBV) lytic antigens are, so far, poorly characterized. Human peptide major histocompatibility complex (MHC) class II multimers provide a means to detect and characterize such rare T cells. Along a screening of T-cell responses to lytic or latent EBV antigens within peripheral blood leukocyte (PBL)- or synovial-derived CD4 T-cell lines, we identified an human leukocyte antigen-DR*0401 (HLA-DR*0401)-restricted epitope derived from BHRF1 (BamHI fragment H rightward open reading frame 1), a viral protein produced during the early stages of the lytic cycle. We show here that T-cell responses to this particular BHRF1 epitope are shared by most EBV-infected DR*0401+ individuals, as BHRF1-specific CD4 T cells could be sorted out from all the DRB*0401 T-cell lines analyzed, using magnetic beads coated with recombinant BHRF1/DR*0401 complexes. Sorting with these peptide MHC class II multimers was very efficient, as the yield of recovery of BHRF1-specific T cells was nearly 100%. Functional analysis of a large number of clones responding to BHRF1/DR*0401 demonstrated their cytolytic action against autologous and allogeneic DR*0401+ EBV-transformed B-lymphoblastoid cell lines (B-LCLs), with 40% to 80% killing efficiency and potent interferon γ production, thus suggesting that this CD4 T-cell population contributes to the control of EBV replication. B-LCL lysis by these T-cell clones was DR*0401 dependent, EBV dependent, and was not merely due to bystander killing. Taken together, these data provide the first demonstration that a lytic antigen can induce a direct cytolytic response against EBV-infected cells.

Original languageEnglish (US)
Pages (from-to)1408-1416
Number of pages9
JournalBlood
Volume103
Issue number4
DOIs
StatePublished - Feb 15 2004
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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