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

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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