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Augmentation of T-cell activation by oscillatory forces and engineered antigen-presenting cells

Fatemeh S. Majedi, Mohammad Mahdi Hasani-Sadrabadi, Timothy J. Thauland, Song Li, Louis-S. Bouchard, Manish J. Butte
doi: https://doi.org/10.1101/580704
Fatemeh S. Majedi
1Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, 90095 USA
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Mohammad Mahdi Hasani-Sadrabadi
1Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, 90095 USA
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Timothy J. Thauland
2Division of Immunology, Allergy, and Rheumatology, Department of Pediatrics, University of California Los Angeles, Los Angeles, CA, 90095 USA
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Song Li
1Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, 90095 USA
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Louis-S. Bouchard
1Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, 90095 USA
3Department of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, CA, 90095 USA
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Manish J. Butte
2Division of Immunology, Allergy, and Rheumatology, Department of Pediatrics, University of California Los Angeles, Los Angeles, CA, 90095 USA
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Abstract

Activation of T cells by antigen presenting cells allows them to proliferate, produce cytokines, and kill infected or cancerous cells. We and others have shown that T cell receptors receive and in fact require mechanical forces from their own movements and the movements of antigen presenting cells. Emulation of T cell activation in vitro allows for the massive expansion of T cells necessary for clinical applications. In this paper, we studied the impact of augmenting novel artificial antigen presenting cells of various sizes and antigenic signal strength with mechanical, oscillatory movement. We showed that dynamic culture roughly doubles signal strength as compared to conventional, static culture. We demonstrated that tuning the strength of signal to a “sweet spot” allows for robust expansion of induced regulatory T cells, which is impeded by approaches that simply maximize activation.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted March 24, 2019.
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Augmentation of T-cell activation by oscillatory forces and engineered antigen-presenting cells
Fatemeh S. Majedi, Mohammad Mahdi Hasani-Sadrabadi, Timothy J. Thauland, Song Li, Louis-S. Bouchard, Manish J. Butte
bioRxiv 580704; doi: https://doi.org/10.1101/580704
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Augmentation of T-cell activation by oscillatory forces and engineered antigen-presenting cells
Fatemeh S. Majedi, Mohammad Mahdi Hasani-Sadrabadi, Timothy J. Thauland, Song Li, Louis-S. Bouchard, Manish J. Butte
bioRxiv 580704; doi: https://doi.org/10.1101/580704

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