Shao Gaohai, Liu Qingjun, Yang Ling, Feng Guibo, Zhao Wang, Huang Zhongyan, Yang Zhao
1Department of orthopedics, Yongchuan Hospital, Chongqing Medical University, Chongqing, 402160 China.
2Department of Neurology and Chongqing key laboratory of cerebravascular disease, Yongchuan Hospital, Chongqing Medical University, Chongqing, 402160 China.
J Inflamm (Lond). 2020 Feb 19;17:10. doi: 10.1186/s12950-020-00240-w. eCollection 2020.
Prediction and identification of cytotoxic T lymphocyte (CTL) epitopes from tumor associated antigens is a crucial step for the development of tumor immunotherapy strategy. Endocan has been identified as antigen overexpressed in various tumors.
In this experiment, we predicted and identified HLA-A2-restricted CTL epitopes from endocan by using the following procedures. Firstly, we predicted the epitopes from the amino acid sequence of endocan by computer-based methods; Secondly, we determined the affinity of the predicted peptide with HLA-A2.1 molecule by peptide-binding assay; Thirdly, we elicited the primary T cell response against the predicted peptides in vitro; Lastly, we tested the specific CTLs toward endocan and HLA-A2.1 positive target cells.
These data demonstrated that peptides of endocan containing residues 4-12 and 9-17 could elicit specific CTLs producing interferon-γ and cytotoxicity.
Therefore, our findings suggested that the predicted peptides were novel HLA-A2.1-restricted CTL epitopes, and might provide promising target for tumor immunotherapy.
从肿瘤相关抗原中预测和鉴定细胞毒性T淋巴细胞(CTL)表位是制定肿瘤免疫治疗策略的关键步骤。内皮抑素已被确定为在多种肿瘤中过度表达的抗原。
在本实验中,我们通过以下步骤从内皮抑素中预测和鉴定HLA - A2限制性CTL表位。首先,我们通过基于计算机的方法从内皮抑素的氨基酸序列中预测表位;其次,我们通过肽结合试验确定预测肽与HLA - A2.1分子的亲和力;第三,我们在体外引发针对预测肽的初始T细胞反应;最后,我们测试了针对内皮抑素和HLA - A2.1阳性靶细胞的特异性CTL。
这些数据表明,包含第4 - 12位和第9 - 17位残基的内皮抑素肽可引发产生干扰素 - γ和细胞毒性的特异性CTL。
因此,我们的研究结果表明,预测的肽是新型的HLA - A2.1限制性CTL表位,可能为肿瘤免疫治疗提供有前景的靶点。