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首页> 外文期刊>Immunology: An Official Journal of the British Society for Immunology >Isolation of human MHC class II-restricted T cell receptors from the autologous T-cell repertoire with potent anti-leukaemic reactivity
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Isolation of human MHC class II-restricted T cell receptors from the autologous T-cell repertoire with potent anti-leukaemic reactivity

机译：从具有强抗白血病反应活性的自体T细胞库中分离人类MHC II类限制性T细胞受体

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Adoptive transfer of T cells genetically modified with tumour-specific T-cell receptors (TCR) is a promising novel approach in the treatment of cancer. We have previously isolated an allorestricted MHC class I-restricted TCR with specificity for Formin-like protein 1 (FMNL1) with potent activity against chronic lymphocytic leukaemia cells. CD4 + T cells have been described to be highly important for tumour elimination although TCR derived from CD4 + T cells with anti-tumour reactivity have been only rarely described. In this study we aimed to isolate MHC class-II-restricted CD4 + T cells and TCR with specificity for leukaemia antigens. We used professional antigen-presenting cells pulsed with the leukaemia-associated and tumour-associated antigen FMNL1 for stimulation of autologous T cells in vitro. We isolated two CD4 + HLA-DR-restricted T-cell clones and T-cell-derived TCR with so far unknown specificity but high reactivity against lymphoma cells and native malignant cells derived from HLA-matched patients with diverse leukaemias. Moreover, characterization of the TCR after TCR gene transfer revealed that specific characteristics of isolated TCR as reactivity in response to Toll-like receptors were transferable on effector cells. Our results have a major impact on the development of novel immunotherapies. They demonstrate that TCR with potent HLA-DR-restricted anti-leukaemic reactivity against so far undefined self-restricted antigens can be isolated from the healthy autorestricted CD4 + T-cell repertoire and these TCR are highly interesting candidate tools for novel immunotherapies.
机译：经肿瘤特异性T细胞受体（TCR）遗传修饰的T细胞的过继转移是治疗癌症的有前途的新方法。我们以前已经分离出了一种对甲型六氢呋喃的限制性I限制的TCR，其对甲酰胺样蛋白1（FMNL1）具有特异性，对慢性淋巴细胞白血病细胞具有有效的活性。尽管很少有人描述CD4 + T细胞对于消除肿瘤非常重要，但源自CD4 + T细胞的具有抗肿瘤反应性的TCR却很少。在这项研究中，我们旨在分离具有MHC II类限制的CD4 + T细胞和对白血病抗原具有特异性的TCR。我们使用与白血病相关和肿瘤相关抗原FMNL1脉冲的专业抗原呈递细胞在体外刺激自体T细胞。我们分离了两个CD4 + HLA-DR限制性T细胞克隆和T细胞来源的TCR，其特异性目前未知，但对来自HLA匹配的患有多种白血病的患者的淋巴瘤细胞和天然恶性细胞具有高反应性。此外，TCR基因转移后的TCR的特征表明，分离的TCR作为响应Toll样受体的反应性的特定特征可以在效应细胞上转移。我们的结果对新型免疫疗法的发展具有重大影响。他们证明，可以从健康的自动限制性CD4 + T细胞库中分离出具有迄今未定义的自我限制性抗原的有效HLA-DR限制性抗白血病反应性的TCR，这些TCR是用于新型免疫疗法的非常有趣的候选工具。

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