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Production of NY-ESO-1 peptide/DRB1*08:03 tetramers and ex vivo detection of CD4 T-cell responses in vaccinated cancer patients

机译:NY-ESO-1 肽/DRB1*08:03 四聚体的生产和疫苗接种癌症患者 CD4 T 细胞反应的体外检测

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摘要

We established CD4 T-cell clones, Mz-1B7, and Ue-21, which recognized the NY-ESO-1 121-138 peptide from peripheral blood mononuclear cells (PBMCs) of an esophageal cancer patient, E-2, immunized with an NY-ESO-1 protein and determined the NY-ESO-1 minimal epitopes. Minimal peptides recognized by Mz-1B7 and Ue-21 were NY-ESO-1125-134 and 124-134, respectively, both in restriction to DRB1*08:03. Using a longer peptide, 122-135, and five other related peptides, including either of the minimal epitopes recognized by the CD4 T-cell clones, we investigated the free peptide/DR recognition on autologous EBV-B cells as APC and peptide/DR tetramer binding. The results showed a discrepancy between them. The tetramers with several peptides recognized by either Mz-1B7 or the Ue-21 CD4 T-cell clone did not bind to the respective clone. On the other hand, unexpected binding of the tetramer with the peptide not recognized by CD4 T-cells was observed. The clone Mz-1B7 did not recognize the free peptide 122-135 on APC, but the peptide 122-135/DRB1*08:03 tetramer bound to the TCR on those cells. The failure of tetramer production and the unexpected tetramer binding could be due to a subtly modified structure of the peptide/DR tetramer from the structure of the free peptide/DR molecule. We also demonstrated that the NY-ESO-1 123-135/DRB1*08:03 tetramer detected ex vivo CD4 T-cell responses in PBMCs from patients after NY-ESO-1 vaccination in immunomonitoring
机译:我们建立了 CD4 T 细胞克隆 Mz-1B7 和 Ue-21,它们识别了来自食管癌患者 E-2 的外周血单核细胞 (PBMC) 的 NY-ESO-1 121-138 肽,用 NY-ESO-1 蛋白免疫并确定了 NY-ESO-1 最小表位。Mz-1B7 和 Ue-21 识别的最小肽分别为 NY-ESO-1125-134 和 124-134,均仅限于 DRB1*08:03。使用更长的肽 122-135 和其他五种相关肽,包括 CD4 T 细胞克隆识别的最小表位之一,我们研究了自体 EBV-B 细胞上的游离肽/DR 识别为 APC 和肽/DR 四聚体结合。结果显示它们之间存在差异。具有 Mz-1B7 或 Ue-21 CD4 T 细胞克隆识别的多个肽的四聚体不与相应的克隆结合。另一方面,观察到四聚体与CD4 T细胞无法识别的肽的意外结合。克隆 Mz-1B7 不识别 APC 上的游离肽 122-135,但识别与这些细胞上的 TCR 结合的肽 122-135/DRB1*08:03 四聚体。四聚体生产失败和意外的四聚体结合可能是由于肽/DR 四聚体的结构与游离肽/DR 分子的结构发生了微妙的修饰。我们还证明,NY-ESO-1 123-135/DRB1*08:03 四聚体在免疫监测中检测了 NY-ESO-1 疫苗接种后患者 PBMC 中的离体 CD4 T 细胞反应

著录项

  • 来源
    《Vaccine》 |2014年第8期|957-964|共8页
  • 作者单位

    Department of Surgery, Osaka University Graduate School of Medicine, Osaka, Japan;

    Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan;

    Department of Respiratory Medicine, Kawasaki Medical School, Okayama, JapanFaculty of Health and Welfare, Kawasaki University of Medical Welfare, Kurashiki 701-0193, Okayama, JapanDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, JapanMedical & Biological Laboratories, Nagano, JapanDepartment of Immunotherapeutics, University of Tokyo Hospital, Tokyo, Japan;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 英语
  • 中图分类 医学免疫学;
  • 关键词

    Tumor immunology; NY-ESO-1; CD4 T-cell; MHC class II tetramer;

    机译:肿瘤免疫学;NY-ESO-1;CD4 T细胞;MHC II类四聚体;

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