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Nanoscale organization of two-dimensional multimeric pMHC reagents with DNA origami for CD8+ T cell detection

Author

Listed:
  • Yueyang Sun

    (East China Normal University)

  • Lu Yan

    (East China Normal University)

  • Jiajia Sun

    (East China Normal University)

  • Mingshu Xiao

    (East China Normal University)

  • Wei Lai

    (East China Normal University)

  • Guangqi Song

    (Zhongshan Hospital of Fudan University)

  • Li Li

    (East China Normal University)

  • Chunhai Fan

    (Shanghai Jiao Tong University)

  • Hao Pei

    (East China Normal University
    Institute of Eco-Chongming)

Abstract

Peptide-MHC (pMHC) multimers have excelled in the detection of antigen-specific T cells and have allowed phenotypic analysis using other reagents, but their use for detection of low-affinity T cells remains a challenge. Here we develop a multimeric T cell identifying reagent platform using two-dimensional DNA origami scaffolds to spatially organize pMHCs (termed as dorimers) with nanoscale control. We show that these dorimers enhance the binding avidity for low-affinity antigen-specific T cell receptors (TCRs). The dorimers are able to detect more antigen-specific T cells in mouse CD8+ T cells and early-stage CD4+CD8+ double-positive thymocytes that express less dense TCRs, compared with the equivalent tetramers and dextramers. Moreover, we demonstrate dorimer function in the analysis of autoimmune CD8+ T cells that express low-affinity TCRs, which are difficult to detect using tetramers. We anticipate that dorimers could contribute to the investigation of antigen-specific T cells in immune T cell function or immunotherapy applications.

Suggested Citation

  • Yueyang Sun & Lu Yan & Jiajia Sun & Mingshu Xiao & Wei Lai & Guangqi Song & Li Li & Chunhai Fan & Hao Pei, 2022. "Nanoscale organization of two-dimensional multimeric pMHC reagents with DNA origami for CD8+ T cell detection," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31684-8
    DOI: 10.1038/s41467-022-31684-8
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    References listed on IDEAS

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    1. Jun Huang & Veronika I. Zarnitsyna & Baoyu Liu & Lindsay J. Edwards & Ning Jiang & Brian D. Evavold & Cheng Zhu, 2010. "The kinetics of two-dimensional TCR and pMHC interactions determine T-cell responsiveness," Nature, Nature, vol. 464(7290), pages 932-936, April.
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