DNA origami demonstrate the unique stimulatory power of single pMHCs as T cell antigens.
Proc Natl Acad Sci U S A
; 118(4)2021 01 26.
Article
em En
| MEDLINE
| ID: mdl-33468643
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
DNA
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Receptores de Antígenos de Linfócitos T
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Linfócitos T CD4-Positivos
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Complexo Principal de Histocompatibilidade
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Células Apresentadoras de Antígenos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Áustria