A dynamic biomimetic model of the membrane-bound CD4-CD3-TCR complex during pMHC disengagement

Rollins, Zachary A.; Faller, Roland; George, Steven C.

doi:10.1016/j.bpj.2023.06.018

Biophysical Journal

2023

DOI: 10.1016/j.bpj.2023.06.018

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A dynamic biomimetic model of the membrane-bound CD4-CD3-TCR complex during pMHC disengagement

Zachary A. Rollins

Roland Faller

Steven C. George

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2024

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Mechanical forces amplify TCR mechanotransduction in T cell activation and function

Jeffreys,

Brockman,

Zhai

et al. 2024

Applied Physics Reviews

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Adoptive T cell immunotherapies, including engineered T cell receptor (eTCR) and chimeric antigen receptor (CAR) T cell immunotherapies, have shown efficacy in treating a subset of hematologic malignancies, exhibit promise in solid tumors, and have many other potential applications, such as in fibrosis, autoimmunity, and regenerative medicine. While immunoengineering has focused on designing biomaterials to present biochemical cues to manipulate T cells ex vivo and in vivo, mechanical cues that regulate their biology have been largely underappreciated. This review highlights the contributions of mechanical force to several receptor–ligand interactions critical to T cell function, with central focus on the TCR–peptide-loaded major histocompatibility complex (pMHC). We then emphasize the role of mechanical forces in (i) allosteric strengthening of the TCR–pMHC interaction in amplifying ligand discrimination during T cell antigen recognition prior to activation and (ii) T cell interactions with the extracellular matrix. We then describe approaches to design eTCRs, CARs, and biomaterials to exploit TCR mechanosensitivity in order to potentiate T cell manufacturing and function in adoptive T cell immunotherapy.

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Mechanical forces amplify TCR mechanotransduction in T cell activation and function

Jeffreys,

Brockman,

Zhai

et al. 2024

Applied Physics Reviews

View full text Add to dashboard Cite

show abstract

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A dynamic biomimetic model of the membrane-bound CD4-CD3-TCR complex during pMHC disengagement

Cited by 1 publication

References 103 publications

Mechanical forces amplify TCR mechanotransduction in T cell activation and function

Mechanical forces amplify TCR mechanotransduction in T cell activation and function

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