Dissecting cytotoxic T cell responses towards the NY-ESO-1 protein by peptide/MHC-specific antibody fragments
Dissecting cytotoxic T cell responses towards the NY-ESO-1 protein by peptide/MHC-specific antibody fragments
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DOI：
10.1002/eji.200425297
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发表时间：
2004-10-01
影响因子：
5.4
通讯作者：
Renner, C
中科院分区：
文献类型：
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作者：
Held, G;Matsuo, M;Renner, C
NY-ESO-1是一种由不同肿瘤类型异常表达的生殖细胞抗原，其激发强烈的体液和细胞免疫应答，代表了用于癌症患者疫苗接种的最有希望的候选物之一。对使用NY-ESO-1衍生肽（157-165和157-167）的疫苗试验中产生的CD 8（+）T细胞的详细分析显示，显性免疫应答针对隐藏表位（159-167），使免疫应答从肿瘤识别转向。只有对NY-ESO-1（157-165）肽的CTL反应性似乎能够裂解表达NY-ESO-1/HLA-A0201的肿瘤细胞。为了更详细地研究NY-ESO-1肽通过肿瘤细胞呈递的过程，我们产生了特异性识别NY-ESO-1（157-165）肽/HLA-A0201复合物的高亲和力（K-D = 60 nM）抗体片段。肽变体如NY-ESO-1（157-167）肽或隐蔽NY-ESO-1159 -167肽未被识别。抗体片段以剂量依赖性方式阻断NY-ESO-1（157-165）肽特异性CD 8（+）T细胞对NY-ESO-1/HLA-A2阳性肿瘤细胞的识别。该抗体片段是一种新型试剂，其以TCR样特异性结合NY-ESO-1（157-165）/HLA-A2复合物，从而区分针对免疫学上有意义的或隐蔽的NY-ESO-1衍生肽的CTL应答。因此，它可能成为开发基于NY-ESO-1的癌症疫苗的有用监测工具。
NY-ESO-1 is a germ cell antigen aberrantly expressed by different tumor types that elicits strong humoral and cellular immune responses, representing one of the most promising candidates for vaccination of cancer patients. A detailed analysis of CD8(+) T cells generated in vaccine trials using NY-ESO-1-derived peptides (157-165 and 157-167) revealed that the dominant immune response was directed against a cryptic epitope (159-167) diverting the immune response from tumor recognition. Only CTL reactivity to the NY-ESO-1(157-165) peptide appeared to be capable of lysing NY-ESO-1/HLA-A0201-expressing tumor cells. To study the process of NY-ESO-1 peptide presentation by tumor cells in more detail we generated a high-affinity (K-D = 60 nM) antibody fragment that specifically recognizes the NY-ESO-1(157-165) peptide/HLA-A0201 complex. Peptide variants such as the NY-ESO-1(157-167) peptide or the cryptic NY-ESO-1 159-167 peptide were not recognized. The antibody fragment blocked in a dose-dependent fashion the recognition of NY-ESO-1/HLA-A2-positive tumor cells by NY-ESO-1(157-165) peptide-specific CD8(+) T cells. This antibody fragment is a novel reagent that binds with TCR-like specificity to the NY-ESO-1(157-165)/HLA-A2 complex thus distinguishing between CTL responses against immunological meaningful or cryptic NY-ESO-1-derived peptides. It may therefore become a useful monitoring tool for the development of NY-ESO-1-based cancer vaccines.