The pivotal task of the immune system is to distinguish between self and foreign antigens. The kinetic proofreading model (KPR) 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 KPR as the available experimental systems fall short of only altering the binding half-lives and keeping other parameters of the ligand-TCR interaction unchanged. We engineered an optogenetic system using the plant photoreceptor phytochrome B to selectively control the dynamics of ligand binding to the TCR by light. Combining experiments with mathematical modeling we find that the ligand-TCR interaction half-life is the decisive factor for activating downstream TCR signaling, substantiating the KPR hypothesis.
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Wolfgang Schamel is the head of the Department of Immunology at the Institute for Biology III and member of the BIOSS Excellence Cluster of the University of Freiburg, Germany.
He studied Biochemistry at the Free University of Berlin and conducted his Diploma thesis at the Weizmann Institute in Israel, working in Yosef Yarden’s group.
Then he moved to Freiburg to the Max Planck Institute for Immunobiology to do his PhD thesis under supervision of Michael Reth.
During his two years of postdoctoral research with Balbino Alarcon at the Centro de Biologia Molecular in Madrid he showed that also the T cell antigen receptor (TCR) can be preclustered, and he contributed significantly to the discovery that the TCR exists in two different CD3 conformational states.
In 2002 he was rewarded with the Emmy-Noether fellowship of the German government and founded his independent research group at the Max Planck Institute for Immunobiology. He continued to work on the TCR and on T cell activation.
Since 2010 he is full professor for Immunology at the University Freiburg.