Epstein-Barr virus nuclear antigen 1-specific CD4+ T cells directly kill Epstein-Barr virus-carrying natural killer and T cells

Ayako Demachi-Okamura, Yoshinori Ito, Yoshiki Akatsuka, Kunio Tsujimura, Yasuo Morishima, Toshitada Takahashi, Kiyotaka Kuzushima

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24 Citations (Scopus)

Abstract

Epstein-Barr virus (EBV) nuclear antigen (EBNA)1 is expressed in every EBV-infected cell, regardless of the state of EBV infection. Although EBNA1 is thought to be a promising antigen for immunotherapy of all EBV-associated malignancies, it is less clear whether EBNA1-specific CD4+ T cells can act as direct effectors. Herein, we investigated the ability of CD4+ T-cell clones induced with overlapping peptides covering the C-terminal region of EBNA1, and identified minimal epitopes and their restricted major histocompatibility complex class II molecules. Of these, a novel epitope, EYHQEGGPD, was found to be presented by DRB1*0401, 0403 and 0406. Five CD4+ T-cell clones recognized endogenously processed and presented antigens on EBV-transformed lymphoblastoid cell lines (LCL) and one example proved capable of killing EBV-carrying natural killer (NK) and T-cell lines derived from patients with chronic active EBV infection (CAEBV). Identification of minimal epitopes facilitates design of peptide-based vaccines and our data suggest that EBNA1-specific CD4+ T cells may play roles as direct effectors for immunotherapy targeting EBV-carrying NK and T-cell malignancies.

Original languageEnglish
Pages (from-to)1633-1642
Number of pages10
JournalCancer science
Volume99
Issue number8
DOIs
Publication statusPublished - 25-08-2008

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Demachi-Okamura, A., Ito, Y., Akatsuka, Y., Tsujimura, K., Morishima, Y., Takahashi, T., & Kuzushima, K. (2008). Epstein-Barr virus nuclear antigen 1-specific CD4+ T cells directly kill Epstein-Barr virus-carrying natural killer and T cells. Cancer science, 99(8), 1633-1642. https://doi.org/10.1111/j.1349-7006.2008.00852.x