@article{mbs:/content/journal/jgv/10.1099/vir.0.82519-0, author = "Ito, Yoshinori and Demachi-Okamura, Ayako and Ohta, Rieko and Akatsuka, Yoshiki and Nishida, Keiko and Tsujimura, Kunio and Morishima, Yasuo and Takahashi, Toshitada and Kuzushima, Kiyotaka", title = "Full-length EBNA1 mRNA-transduced dendritic cells stimulate cytotoxic T lymphocytes recognizing a novel HLA-Cw*0303- and -Cw*0304-restricted epitope on EBNA1-expressing cells", journal= "Journal of General Virology", year = "2007", volume = "88", number = "3", pages = "770-780", doi = "https://doi.org/10.1099/vir.0.82519-0", url = "https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.82519-0", publisher = "Microbiology Society", issn = "1465-2099", type = "Journal Article", abstract = "Epstein–Barr virus (EBV)-encoded nuclear antigen 1 (EBNA1) is an attractive target for immunotherapy against EBV-associated malignancies because it is expressed in all EBV-positive cells. Although CD8+ cytotoxic T-lymphocyte (CTL) epitope presentation is largely prevented by its glycine–alanine-repeat domain (GAr), the use of mRNA-transduced dendritic cells (DCs) would offer the advantage of priming EBNA1-specific CTLs. After stimulation with GAr-containing EBNA1-transduced monocyte-derived DCs, two EBNA1-specific CTL clones, B5 and C6, were isolated successfully from a healthy donor. These CTLs recognize peptides in the context of HLA-B*3501 and HLA-Cw*0303, respectively. A novel epitope, FVYGGSKTSL, was then identified, presented by both HLA-Cw*0303 and -Cw*0304, which are expressed by >35 % of Japanese, >20 % of Northern Han Chinese and >25 % of Caucasians. The mixed lymphocyte–peptide culture method revealed that FVYGGSKTSL-specific CTL-precursor frequencies in HLA-Cw*0303- or -Cw*0304-positive donors were between 1×10−5 and 1×10−4 CD8+ T cells. Moreover, both CTL clones inhibited growth of HLA-matched EBV-transformed B lymphocytes in vitro, and B5 CTLs produced a gamma interferon response to EBNA1-expressing gastric carcinoma cells in the context of HLA-Cw*0303. These data demonstrate that EBNA1 mRNA-transduced DCs may be useful tools for inducing EBNA1-specific CTLs that might be of clinical interest for CTL therapy of EBV-associated malignancies.", }