In vitro stimulation of CD8 and CD4 T cells by dendritic cells loaded with a complex of cholesterol-bearing hydrophobized pullulan and NY-ESO-1 protein:: Identification of a new HLA-DR15-binding CD4 T-cell epitope
In vitro stimulation of CD8 and CD4 T cells by dendritic cells loaded with a complex of cholesterol-bearing hydrophobized pullulan and NY-ESO-1 protein:: Identification of a new HLA-DR15-binding CD4 T-cell epitope
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DOI：
10.1158/1078-0432.ccr-05-1900
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发表时间：
2006-03-15
影响因子：
11.5
通讯作者：
Nakayama, E
中科院分区：
文献类型：
--
作者：
Hasegawa, K;Noguchi, Y;Nakayama, E
目的：NY-ESO-1属于一类癌症/睾丸抗原，已被证明在癌症患者中具有免疫原性。我们合成了带有胆固醇的疏水化普鲁兰多糖和NY-ESO-1蛋白（CHP/ESO）的复合物，并研究了以自体CHP/ESO负载的树突状细胞作为抗原呈递细胞对健康供体外周血单核细胞的CD8和CD4 T细胞的体外刺激。实验设计：通过针对自体EBV-B的IFNγELISPOT测定来确定CD8或CD4 T细胞的体外刺激以牛痘/NY-ESO-1重组病毒或野生型牛痘病毒感染的细胞为靶标，通过ELISA测定分泌的IFNγ。结果：诱导出NY-ESO-1特异性CD8和CD4 T细胞。在表达 HLA-A2 的供体中，用负载 CHP/ESO 的树突状细胞刺激的 CD8 T 细胞识别自然加工的 NY-ESO-1(157-165)（一种 HLA-A2 结合 CD8 T 细胞表位）。 NY-ESO-1 CD4 T 细胞为 Th1 型。我们鉴定了一个新的 HLA-DR15 结合 CD4 T 细胞表位 NY-ESO-1(37-50)。结论：这些发现表明 CHP/ESO 是一种有前途的针对 NY-ESO-1 的多价癌症疫苗。
Purpose: NY-ESO-1 belongs to a class of cancer/testis antigens and has been shown to be immunogenic in cancer patients. We synthesized a complex of cholesterol-bearing hydrophobized pullulan and NY-ESO-1 protein (CHP/ESO) and investigated the in vitro stimulation of CD8 and CD4 T cells from peripheral blood mononuclear cells in healthy donors with autologous CHP/ESO-loaded dendritic cells as antigen-presenting cells.Experimental Design: In vitro stimulation of CD8 or CD4 T cells was determined by IFN gamma ELISPOT assays against autologous EBV-B cells infected with vaccinia/NY-ESO-1 recombinant virus or wild-type vaccinia virus as targets and by ELISA measuring secreted IFN gamma.Results: NY-ESO-1-specific CD8 and CD4 T cells were induced. In a donor expressing HLA-A2, CD8 T cells stimulated with CHP/ESO-loaded dendritic cells recognized naturally processed NY-ESO-1(157-165), an HLA-A2- binding CD8 T cell epitope. NY-ESO-1 CD4 T cells were Th1-type. We identified a new HLA-DR15-binding CD4 T cell epitope, NY-ESO-1(37-50).Conclusions: These findings indicate that CHP/ESO is a promising polyvalent cancer vaccine targeting NY-ESO-1.