Tue, 25/02/2020 - 14:15
,
Campus SB, Building E2 6 Room E.04

Prof. Dr. Wolfgang Schamel
(
Host: Prof. Dr. Ar├ínzazu del Campo
)
Institute of Biology III (Molecular Immunology) and BIOSS Centre for Biological Signalling Studies, University of Freiburg Centre of Chronic Immunodeficiency, University Medical Centre Freiburg

Optogenetics: Light-controlled activation of the T cell receptor reveals kinetic proofreading

The immune system distinguishes between self and foreign antigens. The kinetic proofreading model proposes that T cells discriminate self from foreign ligands by the different ligand binding half-lives to the T cell receptor (TCR). It is challenging to test the kinetic proofreading model as the available experimental systems fall short of only altering the binding half-lives and keeping other parameters of the interaction unchanged. We engineered an optogenetic system using the plant photoreceptor phytochrome B (PhyB) as a ligand to selectively control the dynamics of ligand binding to the TCR by light. This opto-ligand-TCR system was combined with the unique property of PhyB to continuously cycle between the binding and non-binding states under red light, with the light intensity determining the cycling rate and thus the binding duration. Mathematical modeling of our experimental datasets showed that indeed the ligand-TCR interaction half-life is the decisive factor for activating downstream TCR signaling, substantiating the kinetic proofreading model.

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