Clustering of stimuli on single-walled carbon nanotube bundles enhances cellular activation.
Functionalized single-walled carbon nanotube bundles (f-bSWNT) adsorbed with T-cell-stimulating antibodies are shown to enhance both the kinetics and magnitude of T cell stimulation compared to the same concentration of free antibodies in solution. This enhancement is unique to f-bSWNT compared to other artificial substrates with high surface area and similar chemistry. We explored the origins of this enhanced activity with FRET microscopy and found the preferential formation of large antibody stimuli clusters (5 to 6 microm) on the surface of functionalized versus untreated nanotubes. This highlights the important aspect that antigen clusters can be formed on f-bSWNT, impacting the potency of the T cell stimulus. Clustering of T cell antigens on artificial substrates impacts the avidity of interaction with cells facilitating rapid stimulation dynamics and an overall greater magnitude of response. These findings support the use of chemically treated nanotube bundles as an efficient substrate for the presentation of antigens and point to their potential in clinical applications involving artificial antigen-presentation for ex vivo T cell expansion in adoptive immunotherapy.
Fadel
Tarek R
TR
Department of Chemical Engineering, Yale University, P.O. Box 208284, New Haven, Connecticut 06520, USA.
Look
Michael
M
Staffier
Peter A
PA
Haller
Gary L
GL
Pfefferle
Lisa D
LD
Fahmy
Tarek M
TM
D000818:Animals; D000906:Antibodies / Q000737:chemistry* / Q000494:pharmacology*; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D031541:Fluorescence Resonance Energy Transfer; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D037742:Nanotubes, Carbon / Q000737:chemistry*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology
D000906:Antibodies; D018106:CD28 Antigens; D017252:CD3 Complex; D037742:Nanotubes, Carbon