Parsing digital or analogue TCR performance through piconewton forces

Area of Science:

• Immunology
• Biophysics
• Molecular Biology

Background:

• T-cell receptors (TCRs) are critical for adaptive immunity, recognizing peptide-MHC complexes (pMHCs) on target cells.
• The physical forces exerted on TCR-pMHC bonds influence T-cell activation and immunosurveillance efficacy.
• Understanding TCR mechanobiology is essential for developing targeted immunotherapies.

Conclusions:

• TCRs can operate via distinct recognition modes, including a highly efficient digital mechanism.
• Digital TCR responses are likely vital for effective immune surveillance, especially against sparsely distributed antigens like neoantigens.
• The digital TCR activation pathway holds significant promise for advancing cancer immunotherapy strategies.