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• W2920773357 endingPage "332" @default.
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• W2920773357 abstract "Early studies of T cell structural biology using X-ray crystallography, surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC) focused on a picture of the αβT cell receptor (αβTCR) component domains and their cognate ligands (peptides bound to MHC molecules, i.e. pMHCs) as static interaction partners. Moving forward requires integrating this corpus of data with dynamic technologies such as NMR, molecular dynamics (MD) simulations and real-time single molecule (SM) studies exemplified by optical tweezers (OT). NMR bridges relevant timescales and provides the potential for an all-atom dynamic description of αβTCR components prior to and during interactions with binding partners. SM techniques have opened up vistas in understanding the non-equilibrium nature of T cell signaling through the introduction of force-mediated binding measurements into the paradigm for T cell function. In this regard, bioforces consequent to T-lineage cell motility are now perceived as placing piconewton (pN)-level loads on single receptor-pMHC bonds to impact structural change and αβT-lineage biology, including peptide discrimination, cellular activation, and developmental progression. We discuss herein essential NMR technologies in illuminating the role of ligand binding in the preT cell receptor (preTCR), the αβTCR developmental precursor, and convergence of NMR, SM and MD data in advancing our comprehension of T cell development. More broadly we review the central hypothesis that the αβTCR is a mechanosensor, fostered by breakthrough NMR-based structural insights. Collectively, elucidating dynamic aspects through the integrative use of NMR, SM, and MD shall advance fundamental appreciation of the mechanism of T cell signaling as well as inform translational efforts in αβTCR and chimeric T cell (CAR-T) immunotherapies and T cell vaccinology." @default.
• W2920773357 created "2019-03-11" @default.
• W2920773357 creator A5002397582 @default.
• W2920773357 creator A5002459777 @default.
• W2920773357 creator A5006030795 @default.
• W2920773357 creator A5013709830 @default.
• W2920773357 creator A5029573911 @default.
• W2920773357 creator A5044619429 @default.
• W2920773357 creator A5044940094 @default.
• W2920773357 creator A5061603084 @default.
• W2920773357 creator A5090569228 @default.
• W2920773357 date "2019-02-27" @default.
• W2920773357 modified "2023-10-14" @default.
• W2920773357 title "NMR: an essential structural tool for integrative studies of T cell development, pMHC ligand recognition and TCR mechanobiology" @default.
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