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Modulating T Cell Activation by Nanopatterned and Micro-Nanopatterned Antigen Arrays

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Deeg,  Janosch
Cellular Biophysics, Max Planck Institute for Medical Research, Max Planck Society;
Biophysical Chemistry, Institute of Physical Chemistry, University of Heidelberg, 69120 Heidelberg, Germany;

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Citation

Deeg, J. (2014). Modulating T Cell Activation by Nanopatterned and Micro-Nanopatterned Antigen Arrays. PhD Thesis, Universität Heidelberg, Heidelberg. Retrieved from http://www.ub.uni-heidelberg.de/archiv/16157.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0015-7E86-6
Abstract
The human immune system is a multi-talented composition of a variety of interacting elements trying to protect the host from any kind of disease. Much research has been done to elucidate a key event of this complex defense strategy, which is the activation of T cells resulting from the formation of a temporary synapse between a T cell and an antigen presenting cell. During this intercellular contact the T cell obtains pathogen-related information in order to initiate specific steps for averting the disease. In the presented work, we introduce a novel, bio-functional substrate system simulating the antigen presenting cell’s surface. The engineered platform provides defined micro- and nano-scaled presentation of crucial proteins as well as control over substrate compliance. This system enables the possibility to investigate T cell activation and synapse formation under controlled conditions. It could be demonstrated that T cells show activation-related behavior when interacting with such substrates; they adhere, polarize and start to release signaling molecules. These events prove that the substrates can substitute for the antigen presenting cell and are able to modulate the activation process of T cells. It was shown that T cells are sensitive to a surface density of 90–140 stimulating molecules per μm2, but only if presented over the entire cell-surface contact area. An adhesive background consisting of proteins which support the adhesion process significantly decrease this threshold value. These insights contribute to a deeper understanding of the complex process of T cell activation and support the development of novel therapies employing the body’s own defense system to control diseases.