Identification of a new HLA-A*0201-restricted cytotoxic T lymphocyte epitope from CML28
Identification of a new HLA-A*0201-restricted cytotoxic T lymphocyte epitope from CML28
复制标题
DOI：
10.1007/s00262-006-0152-8
复制
发表时间：
2006-12-01
影响因子：
5.8
通讯作者：
Wu, Yu-Zhang
中科院分区：
文献类型：
--
作者：
Han, Jun-Feng;Zhao, Ting-Ting;Wu, Yu-Zhang
从其他肿瘤抗原中鉴定细胞毒性T淋巴细胞（CTL）表位对于恶性肿瘤特异性免疫治疗的发展至关重要。CML28是最近发现的一种来自慢性骨髓性白血病的癌睾丸（CT）抗原，被认为是肿瘤特异性免疫治疗的一个有希望的靶点。由于HLA-A*0201是中国人最常见的组织相容性分子之一，我们的目标是鉴定HLA-A*0201所呈现的CML28肽。使用基于计算机的程序预测cml28衍生的抗原肽组。合成了4个预测得分最高的多肽，并测试了它们与HLA-A*0201分子的结合亲和力。然后对这些肽的免疫原性进行评估，以在体外（来自4个健康HLA-A*0201（+）供体的pbmc）和体内HLA-A*0201转基因小鼠中引发由ctl介导的特异性免疫应答。其中一种被测试的肽CML28（(173-181)）在体外和体内诱导肽特异性ctl，它们可以特异性分泌ifn - γ并裂解内源性表达CML28抗原和CML28（173-181）脉冲jurcat - a2 /Kb细胞的主要组织相容性复合物（MHC）匹配的肿瘤细胞系。这些结果表明CML28（173-181）是一个天然加工的带有HLA-A*0201基序的CTL表位，在体外和体内都具有良好的免疫原性。由于CML28在除慢性髓性白血病外的多种组织学肿瘤中表达，我们提出新发现的表位CML28（173-181）将潜在地用于基于多肽的癌症特异性免疫治疗，针对广泛的肿瘤。
Identification of cytotoxic T lymphocyte (CTL) epitopes from additional tumor antigens is essential for the development of specific immunotherapy of malignant tumors. CML28, a recently discovered cancer-testis (CT) antigen from chronic myelogenous leukemia, is considered to be a promising target of tumor-specific immunotherapy. Because HLA-A*0201 is one of the most common histocompatibility molecule in Chinese, we aim at identifying CML28 peptides presented by HLA-A*0201. A panel of CML28-derived antigenic peptides was predicted using a computer-based program. Four peptides with highest predicted score were synthesized and tested for their binding affinities to HLA-A*0201 molecule. Then these peptides were assessed for their immunogenicity to elicit specific immune responses mediated by CTLs both in vitro, from PBMCs sourced from four healthy HLA-A*0201(+) donors, and in vivo, in HLA-A*0201 transgenic mice. One of the tested peptides, CML28((173-181)), induced peptide-specific CTLs in vitro as well as in vivo, which could specifically secrete IFN-gamma and lyse major histocompatibility complex (MHC)-matched tumor cell lines endogenously expressing CML28 antigen and CML28(173-181) pulsed Jurkat-A2/Kb cells, respectively. These results demonstrate that CML28(173-181) is a naturally processed and presented CTL epitope with HLA-A*0201 motif and has a promising immunogenicity both in vitro and in vivo. As CML28 is expressed in a large variety of histological tumors besides chronic myelogenous leukemia, we propose that the newly identified epitope, CML28(173-181), would be of potential use in peptide-based, cancer-specific immunotherapy against a broad spectrum of tumors.