A single-amino acid substitution in the adaptor LAT accelerates TCR proofreading kinetics and alters T-cell selection, maintenance and function.
Journal
Nature immunology
ISSN: 1529-2916
Titre abrégé: Nat Immunol
Pays: United States
ID NLM: 100941354
Informations de publication
Date de publication:
04 2023
04 2023
Historique:
received:
01
09
2022
accepted:
25
01
2023
medline:
3
4
2023
pubmed:
15
3
2023
entrez:
14
3
2023
Statut:
ppublish
Résumé
Mature T cells must discriminate between brief interactions with self-peptides and prolonged binding to agonists. The kinetic proofreading model posits that certain T-cell antigen receptor signaling nodes serve as molecular timers to facilitate such discrimination. However, the physiological significance of this regulatory mechanism and the pathological consequences of disrupting it are unknown. Here we report that accelerating the normally slow phosphorylation of the linker for activation of T cells (LAT) residue Y136 by introducing an adjacent Gly135Asp alteration (LAT
Identifiants
pubmed: 36914891
doi: 10.1038/s41590-023-01444-x
pii: 10.1038/s41590-023-01444-x
pmc: PMC10063449
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Receptors, Antigen, T-Cell
0
Phosphoproteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
676-689Subventions
Organisme : NIAID NIH HHS
ID : K08 AI137209
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Informations de copyright
© 2023. The Author(s).
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