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

EB病毒（EBV）核抗原（EBNA）1在每个EBV感染的细胞中表达，无论EBV感染的状态如何。尽管EBNA 1被认为是一种有希望用于所有EBV相关恶性肿瘤免疫治疗的抗原（Ag），但EBNA 1特异性CD4^+ T细胞是否可以作为直接效应细胞尚不清楚。在此，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。在这些表位中，发现一种新的表位由DRB 1 ^*0401、0403和0406呈递。5个CD4^+ T细胞克隆能够识别内源性加工的抗原，并将其呈递给EBV转化的淋巴母细胞系，其中一个克隆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基于肽的疫苗的设计，我们的数据表明，EBNA1特异性CD4^+ T细胞可能在靶向携带EBV的NK和T细胞恶性肿瘤的免疫治疗中发挥直接效应。

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.