Separating T Cell Targeting Components onto Magnetically Clustered Nanoparticles Boosts Activation

Alyssa K. Kosmides, Kevin Necochea, John W. Hickey, Jonathan P Schneck

Research output: Contribution to journalArticle

Abstract

T cell activation requires the coordination of a variety of signaling molecules including T cell receptor-specific signals and costimulatory signals. Altering the composition and distribution of costimulatory molecules during stimulation greatly affects T cell functionality for applications such as adoptive cell therapy (ACT), but the large diversity in these molecules complicates these studies. Here, we develop and validate a reductionist T cell activation platform that enables streamlined customization of stimulatory conditions. This platform is useful for the optimization of ACT protocols as well as the more general study of immune T cell activation. Rather than decorating particles with both signal 1 antigen and signal 2 costimulus, we use distinct, monospecific, paramagnetic nanoparticles, which are then clustered on the cell surface by a magnetic field. This allows for rapid synthesis and characterization of a small number of single-signal nanoparticles which can be systematically combined to explore and optimize T cell activation. By increasing cognate T cell enrichment and incorporating additional costimulatory molecules using this platform, we find significantly higher frequencies and numbers of cognate T cells stimulated from an endogenous population. The magnetic field-induced association of separate particles thus provides a tool for optimizing T cell activation for adoptive immunotherapy and other immunological studies.

Original languageEnglish (US)
Pages (from-to)1916-1924
Number of pages9
JournalNano Letters
Volume18
Issue number3
DOIs
StatePublished - Mar 14 2018

Fingerprint

T-cells
acceleration (physics)
Chemical activation
activation
Nanoparticles
nanoparticles
Molecules
platforms
molecules
therapy
Magnetic fields
cells
T-Cell Antigen Receptor
antigens
Antigens
stimulation
magnetic fields
Association reactions
optimization
Chemical analysis

Keywords

  • artificial antigen presenting cell
  • CD8+ T cell
  • immune synapse
  • Immunotherapy
  • magnetic clustering
  • nanoparticle

ASJC Scopus subject areas

  • Bioengineering
  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics
  • Mechanical Engineering

Cite this

Separating T Cell Targeting Components onto Magnetically Clustered Nanoparticles Boosts Activation. / Kosmides, Alyssa K.; Necochea, Kevin; Hickey, John W.; Schneck, Jonathan P.

In: Nano Letters, Vol. 18, No. 3, 14.03.2018, p. 1916-1924.

Research output: Contribution to journalArticle

Kosmides, Alyssa K. ; Necochea, Kevin ; Hickey, John W. ; Schneck, Jonathan P. / Separating T Cell Targeting Components onto Magnetically Clustered Nanoparticles Boosts Activation. In: Nano Letters. 2018 ; Vol. 18, No. 3. pp. 1916-1924.
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