A bead-based method for high-throughput mapping of the sequence- and force-dependence of T cell activation
Year: 2022
Type: article
Abstract: Adaptive immunity relies on T lymphocytes that use αβ T-cell receptors (TCRs) to discriminate amongst peptides presented by MHC molecules (pMHCs). An enhanced ability to screen for pMHCs capable of inducing robust T-cell responses could have broad applications in diagnosing and treating immune diseases. T-cell activation in vivo relies on biomechanical forces to trigger activation by sparse antigenic pMHCs. However, in vitro screening tests potential pMHCs without force and at high (non-physiological) pMHC densities and thus often fails to predict potent agonists in vivo. Here, we present a technology that uses biomechanical force to initiate T-cell triggering in high throughput. BATTLES (Biomechanically-Assisted T-cell Triggering for Large-scale Exogenous-pMHC Screening) displays candidate pMHCs on spectrally encoded ‘smart beads’ capable of applying physiological loads to T cells, facilitating exploration of the force- and sequence-dependent landscape of T-cell responses. BATTLES can be used to explore basic T-cell mechanobiology and T cell-based immunotherapies.
Source: Nature Methods
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Funders: National Science Foundation, Howard Hughes Medical Institute, U.S. Department of Health and Human Services, Alfred P. Sloan Foundation, Cancer Research Institute, G. Harold and Leila Y. Mathers Foundation, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, National Institutes of Health, Stanford Bio-X, Natural Sciences and Engineering Research Council of Canada, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, Division of Electrical, Communications and Cyber Systems
Awards: G1333989588, G1453231909, G1502681674, A Novel Platform for Synthesis of Programmable Proteome-Scale Peptide Bead Arrays, G2348990056, G2521557779, Leveraging spectral encoding for high dimensional biological multiplexing, NNCI: Stanford University - SNSF, SNF, MAF, EMF, G4248490717, Structural correlates of T cell receptor signaling, G7955158285, G8035434472, Understanding Influenza and SARS-CoV-2 vaccine responses, in vivo and in vitro
OpenAlex ID: W4294637049