Molecular design of the γδT cell receptor ectodomain encodes biologically fit ligand recognition in the absence of mechanosensing.
Amino Acid Sequence
Animals
Gene Expression Profiling
Humans
Ligands
Mechanotransduction, Cellular
Mice
Protein Domains
Protein Stability
Protein Structure, Secondary
Receptors, Antigen, T-Cell, alpha-beta
/ chemistry
Receptors, Antigen, T-Cell, gamma-delta
/ chemistry
Signal Transduction
Single Molecule Imaging
T-Lymphocytes
/ metabolism
Thymocytes
/ metabolism
Thymus Gland
/ metabolism
Transcriptome
/ genetics
T cell activation
T cell receptor
mechanosensor
optical tweezers
γδT cells
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
29 06 2021
29 06 2021
Historique:
entrez:
26
6
2021
pubmed:
27
6
2021
medline:
15
12
2021
Statut:
ppublish
Résumé
High-acuity αβT cell receptor (TCR) recognition of peptides bound to major histocompatibility complex molecules (pMHCs) requires mechanosensing, a process whereby piconewton (pN) bioforces exert physical load on αβTCR-pMHC bonds to dynamically alter their lifetimes and foster digital sensitivity cellular signaling. While mechanotransduction is operative for both αβTCRs and pre-TCRs within the αβT lineage, its role in γδT cells is unknown. Here, we show that the human DP10.7 γδTCR specific for the sulfoglycolipid sulfatide bound to CD1d only sustains a significant load and undergoes force-induced structural transitions when the binding interface-distal γδ constant domain (C) module is replaced with that of αβ. The chimeric γδ-αβTCR also signals more robustly than does the wild-type (WT) γδTCR, as revealed by RNA-sequencing (RNA-seq) analysis of TCR-transduced
Identifiants
pubmed: 34172580
pii: 2023050118
doi: 10.1073/pnas.2023050118
pmc: PMC8256041
pii:
doi:
Substances chimiques
Ligands
0
Receptors, Antigen, T-Cell, alpha-beta
0
Receptors, Antigen, T-Cell, gamma-delta
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : P01 AI143565
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI073922
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI115698
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI136301
Pays : United States
Informations de copyright
Copyright © 2021 the Author(s). Published by PNAS.
Déclaration de conflit d'intérêts
The authors declare no competing interest.
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