Research of Epstein-Barr virus-specific T cell immunity targeting the virus-positive cancer

针对病毒阳性癌症的 Epstein-Barr 病毒特异性 T 细胞免疫研究

• 批准号: 17590428
• 负责人: KUZUSHIMA Kiyotaka
• 金额: $ 2.24万
• 依托单位: Aichi Cancer Center Research Institute
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590428/
• 关键词: Epstein-Barr virus; CD4^+ T cells; EBNA1; HLA; lymphoma; 細胞傷害性Tリンパ; ヘルパーT細胞; EBNA; 細胞傷害性Tリンパ球; 胃癌; 上咽頭癌; ホジキンリンパ腫

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 (Ag) for immunotherapy of all EBV-associated malignancies, it is less clear whether EBNA1-specific CD4^+ T cells can act as direct effectors. Here, 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 MHC class II molecules. Of these, a novel epitope was found to be is presented by DRB1^*0401, 0403, and 0406. Five CD4^+ T cell clones recognized endogenously processed and presented antigens on EBV-transformed lymphoblastoid cell lines and one example proved capable of killing EBV-carrying NK and T cell lines derived from patients with chronic active EBV infection. 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.

eb病毒（EBV）核抗原（EBNA） 1在每个感染EBV的细胞中表达，与EBV感染状态无关。尽管EBNA1被认为是一种有希望的抗原（Ag），用于所有ebv相关恶性肿瘤的免疫治疗，但EBNA1特异性CD4^+ T细胞是否可以作为直接效应器尚不清楚。在这里，我们研究了覆盖EBNA1 c端区域的重叠肽诱导CD4^+ T细胞克隆的能力，并鉴定了最小表位及其限制性MHC II类分子。其中，发现DRB1^*0401、0403和0406存在一个新的表位。5个CD4^+ T细胞克隆在EBV转化的淋巴母细胞细胞系上内源性加工和呈递抗原，其中一个被证明能够杀死来自慢性活动性EBV感染患者的携带EBV的NK和T细胞系。最小表位的鉴定有助于设计基于肽的疫苗，我们的数据表明ebna1特异性CD4^+ T细胞可能在针对携带ebna1的NK和T细胞恶性肿瘤的免疫治疗中发挥直接效应。

项目成果

Retroviral vector backbone immunogenicity: identification of cytotoxic T-cell epitopes in retroviral vector-packaging sequences

• DOI: 10.1038/sj.gt.3302406
• 发表时间: 2005-02-01
• 期刊: GENE THERAPY
• 影响因子: 5.1
• 作者: Kondo, E;Akatsuka, Y;Takahashi, T
• 通讯作者: Takahashi, T

Bone marrow may be a reservoir of long-lived memory T cells specific for minor histocompatibility antigen.

骨髓可能是对次要组织相容性抗原具有特异性的长寿命记忆 T 细胞的储存库。

• 发表时间: 2006
• 期刊: Br J Haematol. 135
• 作者: Akatsuka Y;Torikai H;Inamoto Y;et al. (全8名1番目)
• 通讯作者: et al. (全8名1番目)

Three Immunoproteasome-Associated Subunits Cooperatively Generate a CTL Epitope of the EBV LMP2A by Overcoming Specific Structures Resistant to Epitope Liberation.

三个免疫蛋白酶体相关亚基通过克服表位释放抵抗的特定结构协同生成 EBV LMP2A 的 CTL 表位。

• 发表时间: 2006
• 期刊: J Virol. 80(2)
• 作者: Daikoku T.;Kudoh A.;Sugaya Y.;Iwahori S.;Shirata N.;Isomura H.;Tsurumi T.;今井章介;Ito Y.
• 通讯作者: Ito Y.

Differences between T cell-type and natural killer cell-type chronic active Epstein-Barr virus infection

• DOI: 10.1086/427239
• 发表时间: 2005-02-15
• 期刊: JOURNAL OF INFECTIOUS DISEASES
• 影响因子: 6.4
• 作者: Kimura, H;Hoshino, Y;Morishima, T
• 通讯作者: Morishima, T

Identification of an HLA-A24-restricted cytotoxic T lymphocyte epitope from human papillomavirus type-16 E6 : the combined effects of bortezomib and interferon-γ on the presentation of a cryptic epitope.

从人乳头瘤病毒 16 型 E6 中鉴定 HLA-A24 限制性细胞毒性 T 淋巴细胞表位：硼替佐米和干扰素-γ 对隐性表位呈递的联合作用。

• 发表时间: 2007
• 期刊: Int J Cancer. 120(3)
• 作者: Sasaki S;Smith JM;Takase K;Okuda K;Ishii N;Takeshita F;Morishima S.
• 通讯作者: Morishima S.