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Multimodal probing of T-cell recognition with hexapod heterostructures.
Huang, Xiaodan; Meng, Lingyuan; Cao, Guoshuai; Prominski, Aleksander; Hu, Yifei; Yang, Chuanwang; Chen, Min; Shi, Jiuyun; Gallagher, Charles; Cao, Thao; Yue, Jiping; Huang, Jun; Tian, Bozhi.
Afiliación
  • Huang X; Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, USA.
  • Meng L; Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, USA.
  • Cao G; Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, USA.
  • Prominski A; Department of Chemistry, University of Chicago, Chicago, IL, USA.
  • Hu Y; Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, USA.
  • Yang C; Pritzker School of Medicine, University of Chicago, Chicago, IL, USA.
  • Chen M; The James Franck Institute, University of Chicago, Chicago, IL, USA.
  • Shi J; Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, USA.
  • Gallagher C; Department of Chemistry, University of Chicago, Chicago, IL, USA.
  • Cao T; Department of Physics, University of Chicago, Chicago, IL, USA.
  • Yue J; Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, USA.
  • Huang J; Department of Chemistry, University of Chicago, Chicago, IL, USA.
  • Tian B; Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, USA. huangjun@uchicago.edu.
Nat Methods ; 21(5): 857-867, 2024 May.
Article en En | MEDLINE | ID: mdl-38374262
ABSTRACT
Studies using antigen-presenting systems at the single-cell and ensemble levels can provide complementary insights into T-cell signaling and activation. Although crucial for advancing basic immunology and immunotherapy, there is a notable absence of synthetic material toolkits that examine T cells at both levels, and especially those capable of single-molecule-level manipulation. Here we devise a biomimetic antigen-presenting system (bAPS) for single-cell stimulation and ensemble modulation of T-cell recognition. Our bAPS uses hexapod heterostructures composed of a submicrometer cubic hematite core (α-Fe2O3) and nanostructured silica branches with diverse surface modifications. At single-molecule resolution, we show T-cell activation by a single agonist peptide-loaded major histocompatibility complex; distinct T-cell receptor (TCR) responses to structurally similar peptides that differ by only one amino acid; and the superior antigen recognition sensitivity of TCRs compared with that of chimeric antigen receptors (CARs). We also demonstrate how the magnetic field-induced rotation of hexapods amplifies the immune responses in suspended T and CAR-T cells. In addition, we establish our bAPS as a precise and scalable method for identifying stimulatory antigen-specific TCRs at the single-cell level. Thus, our multimodal bAPS represents a unique biointerface tool for investigating T-cell recognition, signaling and function.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Activación de Linfocitos / Linfocitos T Límite: Animals / Humans Idioma: En Revista: Nat Methods Asunto de la revista: TECNICAS E PROCEDIMENTOS DE LABORATORIO Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Activación de Linfocitos / Linfocitos T Límite: Animals / Humans Idioma: En Revista: Nat Methods Asunto de la revista: TECNICAS E PROCEDIMENTOS DE LABORATORIO Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos