title: Epstein-Barr virus nuclear antigen 1-specific CD4+ T cells directly kill Epstein-Barr virus-carrying natural killer and T cells.
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.
authors.affiliation: Division of Immunology, Aichi Cancer Center Research Institute, Nagoya, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Demachi-Okamura
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ito
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Akatsuka
authors.forename: Kunio
authors.initials: K
authors.lastname: Tsujimura
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Morishima
authors.forename: Toshitada
authors.initials: T
authors.lastname: Takahashi
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Kuzushima