Department of Neurology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China.
J Neurooncol. 2013 Aug;114(1):51-8. doi: 10.1007/s11060-013-1167-6. Epub 2013 Jun 11.
Identification of cytotoxic T lymphocyte (CTL) epitopes from additional tumor antigens is essential for the development of specific immunotherapy of malignant tumors. Neuritin, a recently discovered antigen overexpressed in astrocytoma, is considered to be a promising target for biological therapy. In the present study, we predicted and identified HLA-A2-restricted CTL epitopes from neuritin by using the following four-step procedure: (1) computer-based epitope prediction from the amino acid sequence of neuritin; (2) peptide-binding assay to determine the affinity of the predicted peptide with HLA-A2.1 molecule; (3) stimulation of primary T cell response against the predicted peptides in vitro; and (4) testing of the induced CTLs toward target cells expressing neuritin and HLA-A2.1. The results demonstrated that effectors induced by peptides of neuritin containing residues 13-21, 121-129 and 4-12 could specifically-secrete interferon-γ and lyse target cells. Our results indicate that these peptides are new HLA-A2.1-restricted CTL epitopes, and may serve as valuable tools for astrocytoma immunotherapy.
鉴定来自其他肿瘤抗原的细胞毒性 T 淋巴细胞 (CTL) 表位对于恶性肿瘤的特异性免疫治疗的发展至关重要。神经丝蛋白是一种在星形细胞瘤中过表达的新发现的抗原，被认为是生物治疗的一个很有前途的靶点。在本研究中，我们通过以下四个步骤从神经丝蛋白中预测和鉴定了 HLA-A2 限制性 CTL 表位：(1) 基于计算机的从神经丝蛋白氨基酸序列预测表位；(2) 肽结合试验以确定预测肽与 HLA-A2.1 分子的亲和力；(3) 在体外针对预测肽的原代 T 细胞反应的刺激；和 (4) 针对表达神经丝蛋白和 HLA-A2.1 的靶细胞的诱导 CTL 的测试。结果表明，含有残基 13-21、121-129 和 4-12 的神经丝蛋白肽诱导的效应物可以特异性分泌干扰素-γ并裂解靶细胞。我们的结果表明这些肽是新的 HLA-A2.1 限制性 CTL 表位，可作为星形细胞瘤免疫治疗的有价值的工具。
