Laboratory Wolfgang Schamel

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The activation of T lymphocytes by pathogens is the critical event in adaptive immunity. Activation is done by the T cell antigen receptor (TCR), which binds to foreign antigens at its extracellular domains and transmits this information into the cell. Consequently, signalling pathways are activated in the cytoplasm that lead to the actiation of the T cell. Our interest are the molecular mechanisms of this activation event. How is the TCR activated ? By which means does the TCR communicate with the intracellular signalling proteins ? How are the signalling proteins interconnected ? And how can we use this information for treatments of human diseases ? Many (if not all) of these processes are regulated by multi-protein complexes. In order to answer our questions, we develop new biochemical techniques, that we use for the identification and analysis of multi-protein complexes on a large scale (quantitative proteomics, systems biology). The methods are used to define the protein complexes that change in time and space within the signaling cascades of the antigen TCR. In the recent years we have determined the stoichiometry of the TCR, by showing that complexes of different sizes co-exist on the cell membrane. Interestingly, they play different roles in T cell activation. Further, we have detected a conformational change at the TCR that is induced by ligand-binding. Together with TCR clustering the conformational change is required for T cell activation. We have developed a new model of TCR triggering that we call the „permissive geometry model“. It unifies so far irreconcilable findings as crystallographic data of the TCR subunits, studies on the geometry of the ligand (MHC peptide), the presence of multimeric TCR on the cell surface and the role of self-peptide MHC in T cell activation. Interstingly, specifically blocking the effectors of the conformational change, allowed us to inhibit T cell activation. Thus, auto-immune diseases could be treated by blocking the conformational change. Lastly, we work on the human CD3g-deficiency. Since CD3g-deficient mice have a completely different phenotype than the human patients, they cannot be used as a model system. Therefore, we have developed a humanized CD3g-deficient mouse strain, that shows the same defects as the human patients, and is now used to study this disease in detail.


University Group Leader

Wolfgang Schamel
phone: -313

schamel@immunbio.mpg.de

1968
born in Bayreuth, Germany.
Undergraduate studies in Biochemistry at the Free University Berlin, Germany and the Weizmann Institute of Science, Rehovot, Israel

1995-1999
PhD studies at the Max Planck Institute of Immunobiology, Freiburg, Germany

2000-2002
Postdoctoral fellow at the Centro de Biologia Molecular "Severo Ochoa", CSIC, Madrid, Spain

2002-2010
Group leader at the Max Planck Institute of Immunobiology, Freiburg, Germany

since 2010
Professor at the Faculty of Biology and the Centre for Chronic Immunodeficiency CCI, University of Freiburg, Germany

 

Project Areas

  • Structure Function Analysis of the T-cell Antigen Receptor

    Structure Function Analysis of the T-cell Antigen Receptor

    Stimulation of the T-cell antigen receptor (TCR-CD3) is a critical event in the activation of T-cells and the initiation of an immune response. We could show...

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  • A conformational change of the TCR-CD3

    A conformational change of the TCR-CD3

    Antigen binding to the TCR-CD3 complex evokes receptor triggering, including phosphorylation of tyrosines in the cytoplasmic tails of the CD3 and z subunits....

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Recent Publications

Group Members