Mechanical forces amplify TCR mechanotransduction in T cell activation and function

Area of Science:

• Immunology
• Biotechnology
• Biophysics

Background:

• Adoptive T cell immunotherapies like CAR and eTCR T cells show promise for hematologic malignancies and solid tumors.
• Immunoengineering has primarily focused on biochemical cues, largely overlooking the role of mechanical forces in T cell biology.

Purpose of the Study:

• To review the critical role of mechanical force in T cell receptor-ligand interactions.
• To highlight the underappreciated influence of mechanical cues on T cell function and immunotherapy.

Main Methods:

• Review of existing literature on mechanical force and T cell receptor interactions.
• Focus on the T cell receptor-peptide-loaded major histocompatibility complex (pMHC) interaction.
• Examination of T cell interactions with the extracellular matrix.

Main Results:

• Mechanical force allosterically strengthens TCR-pMHC interactions, enhancing ligand discrimination for T cell activation.
• Mechanical forces are crucial for T cell interactions with the extracellular matrix.
• TCR mechanosensitivity plays a key role in T cell antigen recognition.

Conclusions:

• Exploiting TCR mechanosensitivity through engineered T cell receptors (eTCRs), chimeric antigen receptors (CARs), and biomaterials can improve T cell manufacturing and function.
• Understanding mechanical cues is vital for advancing adoptive T cell immunotherapy.