Epstein-Barr virus (EBV) latent membrane protein-1-specific cytotoxic T lymphocytes targeting EBV-carrying natural killer cell malignancies

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

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Epstein-Barr virus (EBV)-encoded latent membrane protein (LMP) 1 is a potential target for immunotherapy of some proportion of Hodgkin's disease cases, nasopharyngeal carcinomas, EBV-associated natural killer (NK)/T lymphomas, and chronic active EBV infection (CAEBV). Since it is unknown whether EBV-infected NK/T cells are susceptible to lysis by LMP1-specific cytotoxic T lymphohcytes (CTL), we here tested the ability of mRNA-transduced antigen-presenting cells (APC) to stimulate rare LMP1-specific CTL. A 43-amino acid N-terminal deletion mutant LMP1 (ΔLMP1) could be efficiently expressed in dendritic cells and CD40-activated B cells upon mRNA electroporation. ΔLMP1-expressing APC were found to stimulate LMP1-specific CTL from a healthy donor and a CTL clone recognized a peptide, IIIILIIFI, presented by HLA-A*0206 molecules. Processing and presentation of the antigenic peptide proved dependent on expression of an immunoproteasome subunit, low-molecular-weight protein-7, as confirmed by RNA interference gene silencing. Furthermore, an EBV-infected NK cell line derived from a patient with CAEBV, and another from an NK lymphoma with enforced HLA-A*0206 expression, were specifically lysed by the CTL. Overall, these data suggest that immunotherapy targeting LMP1 in EBV-associated NK lymphomas and CAEBV might serve as an alternative treatment modality.

Original languageEnglish
Pages (from-to)593-602
Number of pages10
JournalEuropean Journal of Immunology
Volume36
Issue number3
DOIs
Publication statusPublished - 01-03-2006
Externally publishedYes

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Cytotoxic T-Lymphocytes
Human Herpesvirus 4
Natural Killer Cells
Epstein-Barr Virus Infections
Lymphoma
HLA-A Antigens
Antigen-Presenting Cells
Immunotherapy
Neoplasms
Messenger RNA
Peptides
Natural Killer T-Cells
Electroporation
Gene Silencing
RNA Interference
Hodgkin Disease
Dendritic Cells
B-Lymphocytes
Clone Cells
Molecular Weight

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Demachi-Okamura, Ayako ; Ito, Yoshinori ; Akatsuka, Yoshiki ; Tsujimura, Kunio ; Morishima, Yasuo ; Takahashi, Toshitada ; Kuzushima, Kiyotaka. / Epstein-Barr virus (EBV) latent membrane protein-1-specific cytotoxic T lymphocytes targeting EBV-carrying natural killer cell malignancies. In: European Journal of Immunology. 2006 ; Vol. 36, No. 3. pp. 593-602.
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Demachi-Okamura, A, Ito, Y, Akatsuka, Y, Tsujimura, K, Morishima, Y, Takahashi, T & Kuzushima, K 2006, 'Epstein-Barr virus (EBV) latent membrane protein-1-specific cytotoxic T lymphocytes targeting EBV-carrying natural killer cell malignancies', European Journal of Immunology, vol. 36, no. 3, pp. 593-602. https://doi.org/10.1002/eji.200535485

Epstein-Barr virus (EBV) latent membrane protein-1-specific cytotoxic T lymphocytes targeting EBV-carrying natural killer cell malignancies. / Demachi-Okamura, Ayako; Ito, Yoshinori; Akatsuka, Yoshiki; Tsujimura, Kunio; Morishima, Yasuo; Takahashi, Toshitada; Kuzushima, Kiyotaka.

In: European Journal of Immunology, Vol. 36, No. 3, 01.03.2006, p. 593-602.

Research output: Contribution to journalArticle

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