Please use this identifier to cite or link to this item: https://doi.org/10.1021/acs.jpclett.1c02240
Title: Single Molecule Force Spectroscopy Reveals Distinctions in Key Biophysical Parameters of alpha beta T-Cell Receptors Compared with Chimeric Antigen Receptors Directed at the Same Ligand
Authors: Banik, Debasis
Hamidinia, Maryam
Brzostek, Joanna 
Wu, Ling
Stephens, Hannah M
MacAry, Paul A
Reinherz, Ellis L
Gascoigne, Nicholas RJ 
Lang, Matthew J
Keywords: Science & Technology
Physical Sciences
Technology
Chemistry, Physical
Nanoscience & Nanotechnology
Materials Science, Multidisciplinary
Physics, Atomic, Molecular & Chemical
Chemistry
Science & Technology - Other Topics
Materials Science
Physics
CATCH BONDS
ANTIBODY
TCR
COMPLEX
Issue Date: 4-Aug-2021
Publisher: AMER CHEMICAL SOC
Citation: Banik, Debasis, Hamidinia, Maryam, Brzostek, Joanna, Wu, Ling, Stephens, Hannah M, MacAry, Paul A, Reinherz, Ellis L, Gascoigne, Nicholas RJ, Lang, Matthew J (2021-08-04). Single Molecule Force Spectroscopy Reveals Distinctions in Key Biophysical Parameters of alpha beta T-Cell Receptors Compared with Chimeric Antigen Receptors Directed at the Same Ligand. JOURNAL OF PHYSICAL CHEMISTRY LETTERS 12 (31) : 7566-7573. ScholarBank@NUS Repository. https://doi.org/10.1021/acs.jpclett.1c02240
Abstract: Chimeric antigen receptor (CAR) T-cell therapies exploit facile antibody-mediated targeting to elicit useful immune responses in patients. This work directly compares binding profiles of CAR and αβ T-cell receptors (TCR) with single cell and single molecule optical trap measurements against a shared ligand. DNA-tethered measurements of peptide-major histocompatibility complex (pMHC) ligand interaction in both CAR and TCR exhibit catch bonds with specific peptide agonist peaking at 25 and 14 pN, respectively. While a conformational transition is regularly seen in TCR-pMHC systems, that of CAR-pMHC systems is dissimilar, being infrequent, of lower magnitude, and irreversible. Slip bonds are observed with CD19-specific CAR T-cells and with a monoclonal antibody mapping to the MHC α2 helix but indifferent to the bound peptide. Collectively, these findings suggest that the CAR-pMHC interface underpins the CAR catch bond response to pMHC ligands in contradistinction to slip bonds for CARs targeting canonical ligands.
Source Title: JOURNAL OF PHYSICAL CHEMISTRY LETTERS
URI: https://scholarbank.nus.edu.sg/handle/10635/239266
ISSN: 1948-7185
1948-7185
DOI: 10.1021/acs.jpclett.1c02240
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