DNA origami demonstrate the unique stimulatory power of single pMHCs as T cell antigens.
Animals
Antigen-Presenting Cells
/ cytology
CD4-Positive T-Lymphocytes
/ cytology
DNA
/ chemistry
Gene Expression
Ligands
Lipid Bilayers
/ chemistry
Lymphocyte Activation
Major Histocompatibility Complex
/ genetics
Mice
Nucleic Acid Conformation
Phosphatidylcholines
/ chemistry
Primary Cell Culture
Protein Binding
Receptors, Antigen, T-Cell
/ chemistry
Signal Transduction
Single-Chain Antibodies
/ chemistry
Spleen
/ cytology
DNA origami
T cell activation
nanobiotechnology
pMHC
serial engagement
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:
26 01 2021
26 01 2021
Historique:
entrez:
20
1
2021
pubmed:
21
1
2021
medline:
10
6
2021
Statut:
ppublish
Résumé
T cells detect with their T cell antigen receptors (TCRs) the presence of rare agonist peptide/MHC complexes (pMHCs) on the surface of antigen-presenting cells (APCs). How extracellular ligand binding triggers intracellular signaling is poorly understood, yet spatial antigen arrangement on the APC surface has been suggested to be a critical factor. To examine this, we engineered a biomimetic interface based on laterally mobile functionalized DNA origami platforms, which allow for nanoscale control over ligand distances without interfering with the cell-intrinsic dynamics of receptor clustering. When targeting TCRs via stably binding monovalent antibody fragments, we found the minimum signaling unit promoting efficient T cell activation to consist of two antibody-ligated TCRs within a distance of 20 nm. In contrast, transiently engaging antigenic pMHCs stimulated T cells robustly as well-isolated entities. These results identify pairs of antibody-bound TCRs as minimal receptor entities for effective TCR triggering yet validate the exceptional stimulatory potency of single isolated pMHC molecules.
Identifiants
pubmed: 33468643
pii: 2016857118
doi: 10.1073/pnas.2016857118
pmc: PMC7848602
pii:
doi:
Substances chimiques
Ligands
0
Lipid Bilayers
0
Phosphatidylcholines
0
Receptors, Antigen, T-Cell
0
Single-Chain Antibodies
0
DNA
9007-49-2
1-palmitoyl-2-oleoylphosphatidylcholine
TE895536Y5
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Austrian Science Fund FWF
ID : V 538
Pays : Austria
Organisme : Wellcome Trust
ID : 100262 Z/12/Z
Pays : United Kingdom
Déclaration de conflit d'intérêts
The authors declare no competing interest.
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