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

Research output: Contribution to journalArticle

23 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

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Epstein-Barr Virus Nuclear Antigens
Natural Killer T-Cells
Human Herpesvirus 4
T-Lymphocytes
Epitopes
Epstein-Barr Virus Infections
Immunotherapy
Clone Cells
Antigens
Transformed Cell Line
Subunit Vaccines
Major Histocompatibility Complex
Neoplasms
Cell Line

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

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
Demachi-Okamura, Ayako ; Ito, Yoshinori ; Akatsuka, Yoshiki ; Tsujimura, Kunio ; Morishima, Yasuo ; Takahashi, Toshitada ; Kuzushima, Kiyotaka. / Epstein-Barr virus nuclear antigen 1-specific CD4+ T cells directly kill Epstein-Barr virus-carrying natural killer and T cells. In: Cancer Science. 2008 ; Vol. 99, No. 8. pp. 1633-1642.
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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, vol. 99, no. 8, pp. 1633-1642. https://doi.org/10.1111/j.1349-7006.2008.00852.x

Epstein-Barr virus nuclear antigen 1-specific CD4+ T cells directly kill Epstein-Barr virus-carrying natural killer and T cells. / Demachi-Okamura, Ayako; Ito, Yoshinori; Akatsuka, Yoshiki; Tsujimura, Kunio; Morishima, Yasuo; Takahashi, Toshitada; Kuzushima, Kiyotaka.

In: Cancer Science, Vol. 99, No. 8, 25.08.2008, p. 1633-1642.

Research output: Contribution to journalArticle

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AU - Demachi-Okamura, Ayako

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AU - Tsujimura, Kunio

AU - Morishima, Yasuo

AU - Takahashi, Toshitada

AU - Kuzushima, Kiyotaka

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