Label-free electronic detection of the antigen-specific T-cell immune response.

Label-free electronic detection of the antigen-specific T-cell immune response.
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抗原特异性 T 细胞免疫反应的无标记电子检测。

DOI:
10.1021/nl801693k
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发表时间:
2008-10
期刊:
影响因子:
10.8
通讯作者:
Fahmy TM
Fahmy TM
中科院分区:
材料科学1区
文献类型:
--
作者:
Stern E;Steenblock ER;Reed MA;Fahmy TM

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抗原特异性t细胞的检测对于许多疾病状态的诊断评估和治疗策略的设计至关重要。对这些细胞的有效监测需要评估其数量和功能反应的技术。目前抗原特异性t细胞的检测包括流式细胞术和功能分析,需要荧光标记,可溶形式的多肽负载主要组织相容性复合体(MHC)。我们证明了纳米级固态互补金属氧化物半导体(CMOS)技术可以用于在刺激后几秒钟内直接,无标记的电子检测抗原特异性t细胞反应。我们的方法依赖于检测由少数t细胞(少至200个)引起的细胞外酸化,其激活是通过触发t细胞抗原受体诱导的。我们发现,非特异性抗cd3刺激触发的t细胞可以在暴露于刺激后10秒内检测到。相比之下,暴露于肽/MHC激动剂后,抗原特异性t细胞反应较慢,反应时间大于40秒。这种技术的速度和灵敏度有可能阐明激活诱导的t细胞反应动力学的新认识。这与它易于集成到传统电子设备中相结合,有可能实现快速临床测试和高通量表位和药物筛选。
Detection of antigen-specific T-cells is critical for diagnostic assessment and design of therapeutic strategies for many disease states. Effective monitoring of these cells requires technologies that assess their numbers as well as functional response. Current detection of antigen-specific T-cells involves flow cytometry and functional assays and requires fluorescently labeled, soluble forms of peptide-loaded major histocompatability complexes (MHC). We demonstrate that nanoscale solid-state complementary metal-oxide-semiconductor (CMOS) technology can be employed to allow direct, label-free electronic detection of antigen-specific T-cell responses within seconds after stimulation. Our approach relies on detection of extracellular acidification arising from a small number of T-cells (as few as ~200), whose activation is induced by triggering the T-cell antigen receptor. We show that T-cell triggering by a nonspecific anti-CD3 stimulus can be detected within 10 s after exposure to the stimulus. In contrast, antigen-specific T-cell responses are slower with response times greater than 40 s after exposure to peptide/MHC agonists. The speed and sensitivity of this technique has the potential to elucidate new understandings of the kinetics of activation-induced T-cell responses. This combined with its ease of integration into conventional electronics potentially enable rapid clinical testing and high-throughput epitope and drug screening.
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发表时间: 2001-02-01
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发表时间: 2001-03-01
期刊: NATURE IMMUNOLOGY
影响因子: 30.5
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