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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Survey of naturally occurring CD4(+) T cell responses against NY-ESO-1 in cancer patients: Correlation with antibody responses
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Survey of naturally occurring CD4(+) T cell responses against NY-ESO-1 in cancer patients: Correlation with antibody responses

机译：癌症患者对NY-ESO-1的天然CD4（+）T细胞应答的调查：与抗体应答的相关性

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摘要

NY-ESO-1 is one of the most immunogenic proteins described in human cancers, based on its capacity to elicit simultaneous antibody and CD8(+) T cell responses in vivo. Although HLA class II restricted epitopes from NY-ESO-1 have been identified, no broad survey has yet established the status of natural CD4(+) T cell responses in cancer patients in relation to CD8(+) and antibody responses. We used a recently developed general strategy for monitoring CD4(+) responses that overcomes the need for prior knowledge of epitope or HLA restriction to analyze a series of 31 cancer patients and healthy donors for the presence of CD4(+) T cells to NY-ESO-1, and related this response to NY-ESO-1 expression in tumor cells and serum antibodies to NY-ESO-1. None of the 18 patients that tested seronegative for NY-ESO-1 had detectable CD4(+) T cell responses. On the contrary, 11 of 13 cancer patients with serum antibodies to NY-ESO-1 had polyclonal CD4(+) T cell responses directed against various known and previously undescribed NY-ESO-1 epitopes. NY-ESO-1 peptide 80-109 was the most immunogenic, with 10 of 11 patients responding to this peptide. We show here that 12-mer determinants from NY-ESO-1 eliciting a CD4(+) T cell response were peptide 87-98 with promiscuous HLA class II presentation, peptide 108-119 restricted by HLA-DP4, and peptides 121-132 and 145-156, both shorter epitopes from previously described HLA-DR4 peptides, also presented by HLA-DR7. This study represents the next step in compiling a comprehensive picture of the adaptive immune response to NY-ESO-1, and provides a general strategy for analyzing the CD4(+) T cell response to other tumor antigens eliciting a humoral immune response. [References: 28]
机译：NY-ESO-1是人类癌症中描述的最具免疫原性的蛋白质之一，基于其在体内引起同时发生的抗体和CD8（+）T细胞反应的能力。尽管已经确定了来自NY-ESO-1的HLA II类限制性表位，但尚无广泛调查确定癌症患者中与CD8（+）和抗体反应相关的天然CD4（+）T细胞反应的状态。我们使用了最近开发的监测CD4（+）反应的通用策略，该策略克服了对表位或HLA限制的先验知识的需要，从而分析了31位癌症患者和健康供体的一系列NY-CD4（+）T细胞的存在ESO-1，并将其与肿瘤细胞中NY-ESO-1表达的反应以及针对NY-ESO-1的血清抗体相关。测试血清阴性的NY-ESO-1的18例患者中没有一个可检测到CD4（+）T细胞反应。相反，在13名具有针对NY-ESO-1血清抗体的癌症患者中，有11名患有针对各种已知和先前未描述的NY-ESO-1表位的多克隆CD4（+）T细胞应答。 NY-ESO-1肽80-109是最具免疫原性的，在11位患者中有10位对此肽有反应。我们在这里显示，从NY-ESO-1引发CD4（+）T细胞反应的12-mer决定簇是具有混杂HLA II类呈递的肽87-98，受HLA-DP4限制的肽108-119和肽121-132 HLA-DR7和HLA-DR4都具有较短的表位和145-156。这项研究代表了下一步对NY-ESO-1的适应性免疫反应的全面整理，并为分析CD4（+）T细胞对其他引发体液免疫反应的肿瘤抗原的反应提供了一般策略。 [参考：28]

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