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

Yueyang Sun, Lu Yan, Jiajia Sun, Mingshu Xiao, Wei Lai, Guangqi Song, Li Li, Chunhai Fan and Hao Pei ()
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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

Nature Communications, 2022, vol. 13, issue 1, 1-11

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-31684-8

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