RT Journal Article SR Electronic(1) A1 Ito, Yoshinori A1 Demachi-Okamura, Ayako A1 Ohta, Rieko A1 Akatsuka, Yoshiki A1 Nishida, Keiko A1 Tsujimura, Kunio A1 Morishima, Yasuo A1 Takahashi, Toshitada A1 Kuzushima, KiyotakaYR 2007 T1 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 JF Journal of General Virology, VO 88 IS 3 SP 770 OP 780 DO https://doi.org/10.1099/vir.0.82519-0 PB Microbiology Society, SN 1465-2099, AB 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., UL https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.82519-0