A DNA Origami-Based Biointerface to Interrogate the Spatial Requirements for Sensitized T-Cell Antigen Recognition

Area of Science:

• Immunology
• Biotechnology
• Nanotechnology

Background:

• T cells (T lymphocytes) detect minute amounts of peptide/MHC complexes (pMHCs) on antigen-presenting cells (APCs).
• Achieving high sensitivity and selectivity despite numerous non-stimulatory pMHCs and moderate T-cell receptor (TCR) affinity remains unclear.
• Understanding TCR engagement requires precise control over physical input parameters within the immunological synapse.

Purpose of the Study:

• To develop and implement a novel biointerface for studying T-cell activation.
• To experimentally define molecular distances between T-cell ligands.
• To correlate ligand spacing with T-cell dynamics, signaling, and response.

Main Methods:

• Utilized DNA origami nanostructures as versatile and rigid platforms.
• Embedded DNA origami as laterally mobile entities within supported lipid bilayers.
• Achieved site-specific and orthogonal functionalization with proteins of interest.

Main Results:

• The biointerface allows precise control over the spatial arrangement of T-cell ligands.
• Enabled correlation of molecular distances with antigen engagement dynamics.
• Facilitated investigation of downstream signaling and T-cell responses.

Conclusions:

• The developed DNA origami biointerface is a powerful tool for dissecting T-cell recognition mechanisms.
• Precise control over ligand presentation is crucial for understanding T-cell sensitivity and selectivity.
• This approach advances experimental interrogation of the immunological synapse.