Identification of human leukemia antigen A*0201-restricted epitopes derived from epidermal growth factor pathway substrate number 8.
Identification of human leukemia antigen A*0201-restricted epitopes derived from epidermal growth factor pathway substrate number 8.
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源自表皮生长因子途径底物 8 号的人白血病抗原 A0201 限制性表位的鉴定
DOI：
10.3892/mmr.2015.3673
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发表时间：
2015-08
影响因子：
3.4
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Tang B;Zhou W;Du J;He Y;Li Y
恶性血液病的T细胞介导的免疫治疗需要选择靶向的肿瘤相关抗原和这些肿瘤蛋白中包含的T细胞表位。表皮生长因子受体途径底物8（Epidermal growth factor receptor pathway substrate 8，EPS 8）在肿瘤的增殖、进展和转移中起着关键作用，在大多数肿瘤中过表达，而在正常组织中表达较低。本研究的目的是通过反向免疫学方法鉴定EPS 8的人类白血病抗原（HLA）-A*0201限制性表位。为了实现这一点，使用计算机算法来预测HLA-A*0201分子结合、蛋白酶体切割模式以及与抗原加工相关的转运蛋白的易位。候选肽通过T2结合亲和力测定和布雷菲德菌素-A衰变测定进行实验验证。采用酶联免疫斑点试验和细胞毒性试验检测了健康志愿者外周血单个核细胞诱导的肽特异性细胞毒性T淋巴细胞（CTL）的功能亲和力。其中P455、P92、P276和P360四个肽段与HLA-A*0201分子具有较高的亲和力和稳定性，它们诱导的特异性CTL对相应的肽段有明显的应答，并分泌IFN-γ。同时，CTL能够以HLA-A*0201限制性方式特异性裂解表达EPS 8的细胞系。本研究证实P455、P92、P276和P360是EPS 8的CTL表位，可用于表位确定的过继性T细胞转移和多表位疫苗设计。
T-cell-mediated immunotherapy of hematological malignancies requires selection of targeted tumor-associated antigens and T-cell epitopes contained in these tumor proteins. Epidermal growth factor receptor pathway substrate 8 (EPS8), whose function is pivotal for tumor proliferation, progression and metastasis, has been found to be overexpressed in most human tumor types, while its expression in normal tissue is low. The aim of the present study was to identify human leukemia antigen (HLA)-A*0201-restricted epitopes of EPS8 by using a reverse immunology approach. To achieve this, computer algorithms were used to predict HLA-A*0201 molecular binding, proteasome cleavage patterns as well as translocation of transporters associated with antigen processing. Candidate peptides were experimentally validated by T2 binding affinity assay and brefeldin-A decay assay. The functional avidity of peptide-specific cytotoxic T lymphocytes (CTLs) induced from peripheral blood mononuclear cells of healthy volunteers were evaluated by using an enzyme-linked immunosorbent spot assay and a cytotoxicity assay. Four peptides, designated as P455, P92, P276 and P360, had high affinity and stability of binding towards the HLA-A*0201 molecule, and specific CTLs induced by them significantly responded to the corresponding peptides and secreted IFN-γ. At the same time, the CTLs were able to specifically lyse EPS8-expressing cell lines in an HLA-A*0201-restricted manner. The present study demon-strated that P455, P92, P276 and P360 were CTL epitopes of EPS8, and were able to be used for epitope-defined adoptive T-cell transfer and multi-epitope-based vaccine design.
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影响因子：
--
作者：
Castelli M;Cappelletti F;Diotti RA;Sautto G;Criscuolo E;Dal Peraro M;Clementi N
通讯作者：
Clementi N
影响因子：
15.9
作者：
Hebeisen, Michael;Baitsch, Lukas;Rufer, Nathalie
通讯作者：
Rufer, Nathalie
影响因子：
3.7
作者：
Brentville VA;Metheringham RL;Gunn B;Durrant LG
通讯作者：
Durrant LG
影响因子：
6.5
作者：
Kang YJ;Zeng W;Song W;Reinhold B;Choi J;Brusic V;Yamashita T;Munshi A;Li C;Minvielle S;Anderson KC;Munshi N;Reinherz EL;Sasada T
通讯作者：
Sasada T
影响因子：
6.4
作者：
Jorgensen, Kasper W.;Rasmussen, Michael;Nielsen, Morten
通讯作者：
Nielsen, Morten