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

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

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)770-780
Number of pages11
JournalJournal of General Virology
Volume88
Issue number3
DOIs
Publication statusPublished - 01-03-2007

Fingerprint

Cytotoxic T-Lymphocytes
Dendritic Cells
Epitopes
Human Herpesvirus 4
Messenger RNA
Alanine
Glycine
Clone Cells
Epstein-Barr Virus Nuclear Antigens
Peptides
T-Lymphocyte Epitopes
HLA-B Antigens
Immunotherapy
Interferon-gamma
EBV-encoded nuclear antigen 1
Monocytes
Neoplasms
Stomach
B-Lymphocytes
Lymphocytes

All Science Journal Classification (ASJC) codes

  • Virology

Cite this

Ito, Yoshinori ; Demachi-Okamura, Ayako ; Ohta, Rieko ; Akatsuka, Yoshiki ; Nishida, Keiko ; Tsujimura, Kunio ; Morishima, Yasuo ; Takahashi, Toshitada ; Kuzushima, Kiyotaka. / 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. In: Journal of General Virology. 2007 ; Vol. 88, No. 3. pp. 770-780.
@article{b711e662a5ef48d0a8591eba660a0c05,
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",
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.",
author = "Yoshinori Ito and Ayako Demachi-Okamura and Rieko Ohta and Yoshiki Akatsuka and Keiko Nishida and Kunio Tsujimura and Yasuo Morishima and Toshitada Takahashi and Kiyotaka Kuzushima",
year = "2007",
month = "3",
day = "1",
doi = "10.1099/vir.0.82519-0",
language = "English",
volume = "88",
pages = "770--780",
journal = "Journal of General Virology",
issn = "0022-1317",
publisher = "Society for General Microbiology",
number = "3",

}

Ito, Y, Demachi-Okamura, A, Ohta, R, Akatsuka, Y, Nishida, K, Tsujimura, K, Morishima, Y, Takahashi, T & Kuzushima, K 2007, '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 of General Virology, vol. 88, no. 3, pp. 770-780. https://doi.org/10.1099/vir.0.82519-0

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. / Ito, Yoshinori; Demachi-Okamura, Ayako; Ohta, Rieko; Akatsuka, Yoshiki; Nishida, Keiko; Tsujimura, Kunio; Morishima, Yasuo; Takahashi, Toshitada; Kuzushima, Kiyotaka.

In: Journal of General Virology, Vol. 88, No. 3, 01.03.2007, p. 770-780.

Research output: Contribution to journalArticle

TY - JOUR

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

AU - Ito, Yoshinori

AU - Demachi-Okamura, Ayako

AU - Ohta, Rieko

AU - Akatsuka, Yoshiki

AU - Nishida, Keiko

AU - Tsujimura, Kunio

AU - Morishima, Yasuo

AU - Takahashi, Toshitada

AU - Kuzushima, Kiyotaka

PY - 2007/3/1

Y1 - 2007/3/1

N2 - 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.

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.

UR - http://www.scopus.com/inward/record.url?scp=33847630103&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33847630103&partnerID=8YFLogxK

U2 - 10.1099/vir.0.82519-0

DO - 10.1099/vir.0.82519-0

M3 - Article

C2 - 17325349

AN - SCOPUS:33847630103

VL - 88

SP - 770

EP - 780

JO - Journal of General Virology

JF - Journal of General Virology

SN - 0022-1317

IS - 3

ER -