DNA nanostructure‐programmed intermembrane spacing to modulate T‐cell immunity

• Published in: Clinical and translational medicine Vol. 13; no. 8; pp. e1379 - n/a
• Main Authors: Du, Yulin, Qiu, Liping, Tan, Weihong
• Format: Journal Article
• Language: English
• Published: Heidelberg John Wiley & Sons, Inc 01.08.2023; John Wiley and Sons Inc; Wiley
• Subjects: Antigens; Clinical medicine; Conflicts of interest; Genetic engineering; Kinases; Microscopy; Phosphorylation; Proteins; Signal transduction
• ISSN: 2001-1326; 2001-1326
• DOI: 10.1002/ctm2.1379

Despite its crucial role in T-cell immunity, there is still controversy regarding the molecular mechanism of how TCR–pMHC binding initiates intracellular ITAM phosphorylation.3 Previous studies have examined the spatial impact of the close-contact zone on TCR triggering process by genetically manipulating the length of pMHC ligand or other membrane proteins.4,5 Whereas, these techniques involve modifications to protein structure and expression, and show difficulty to accurately assess the linear correlation between intermembrane distance and TCR signalling strength. Based on total internal reflection fluorescence microscopy (TIRFM) and transmission electron microscopy (TEM) imaging, we showed that these DNJs can precisely tune the intermembrane spacing to the desired values (Figure 1B,C). Notably, reducing the intermembrane distance at the APC–T-cell interface to less than 10 nm could significantly enhance T-cell activation, thus expanding the opportunities for the study of T-cell immunity and further applying for the development of novel therapies for immune-related disorders. [...]it exhibits significant potential in promoting targeted T-cell responses in the field of immunotherapy.