Shanghai Key Laboratory of Green Chemistry and Chemical Processes, School of Chemistry and Molecular Engineering, East China Normal University, 500 Dongchuan Road, 200241, Shanghai, China.
Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai, China.
Nat Commun. 2022 Jul 7;13(1):3916. doi: 10.1038/s41467-022-31684-8.
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 CD4CD8 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.
肽-MHC (pMHC) 多聚体在检测抗原特异性 T 细胞方面表现出色，并允许使用其他试剂进行表型分析，但它们在检测低亲和力 T 细胞方面仍存在挑战。在这里，我们使用二维 DNA 折纸支架开发了一种多聚体 T 细胞识别试剂平台，用于空间组织 pMHC（称为 dorimers），具有纳米级控制。我们表明，这些 dorimers 增强了与低亲和力抗原特异性 T 细胞受体 (TCR) 的结合亲和力。与等效的四聚体和 dextramers 相比，dorimers 能够在表达密度较低的 TCR 的小鼠 CD8 T 细胞和早期 CD4CD8 双阳性胸腺细胞中检测到更多的抗原特异性 T 细胞。此外，我们证明了 dorimer 在分析表达低亲和力 TCR 的自身免疫性 CD8 T 细胞中的功能，这些细胞很难用四聚体检测到。我们预计 dorimers 将有助于研究免疫 T 细胞功能或免疫治疗应用中的抗原特异性 T 细胞。
