Multivalent Presentation of TCRs on DNA Nanostructures as a Sensitive Probe for pMHC Detection
Details
Publication Year 2025-06-20,Volume 8,Issue #24,Page 12490-12497
Journal Title
ACS Applied Nano Materials
Publication Type
Research article
Abstract
Dendritic cells (DCs) are key regulators of immune responses, presenting antigen-derived peptides on major histocompatibility complexes (pMHCs) to T cells for recognition via their T cell receptors (TCRs). Despite the weak intrinsic affinity of the TCR-pMHC interaction, T cells exhibit remarkable specificity and sensitivity in detecting and responding to antigenic peptides even at very low concentrations. However, directly probing pMHC complexes on cell surfaces remains technically challenging, particularly when they are presented at low levels due to the limited sensitivity and/or specificity of existing probes. Here, we leveraged the structural nanoscale precision of DNA origami to transform the high specificity, but low intrinsic affinity, of TCRs into high affinity probes with programmable binding profiles. We demonstrate that our approach has the potential to perform better than conventional TCR-like antibodies in sensitivity, providing a promising strategy for facilitating the study of antigen presentation.
Publisher
American Chemical Society
Department(s)
Laboratory Research
Open Access at Publisher's Site
https://doi.org/10.1021/acsanm.5c01296
Terms of Use/Rights Notice
Refer to copyright notice on published article.


Creation Date: 2026-06-16 02:11:45
Last Modified: 2026-06-16 02:11:53
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