FOR2799

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"Receiving and Translating Signals via the γδ T Cell Receptor"

  

γδ T cells were discovered over 30 years ago. However, in  contrast to their MHC-restricted αβ T cell counterparts, their place in  cellular immunity of vertebrates is not yet defined. Over the past few  years, the visibility and scientific output of the γδ T cell field has  rapidly gained momentum due to outstanding new findings regarding the  identification of potential ligands for the γδ TCR, insights into the  role of γδ T cells in the control of infectious diseases, and due to the  recognition of γδ T cells as a potential cellular therapy against  tumors. Thus, γδ T cell research is a hot topic with a lot of potential  for translation into clinical application. Notably, several German  research groups have recently contributed important new findings to the  γδ T cell field. Together, we are therefore confident that that it is  the right time to join our forces within the frame of a DFG Research  Unit.
In this proposal, we hypothesize that recognition of cognate  antigen via the γδ TCR leads to intracellular signal transduction and γδ  T cell activation, differentiation and execution of effector functions,  and activated γδ T cells proliferate and thereby focus the γδ T cell  repertoire. The specific aims of this consortium are to cooperatively  monitor and define how γδ T cells participate in immune responses  against cancer and infections, to better understand how the γδ TCR is  activated, and to investigate the consequences of γδ T cell activation.  To this end, our portfolio ranges from clinical observational studies to  the investigation of basic biochemical questions and from experimental  in vivo studies back to translational clinical approaches. We will  exchange and jointly apply our complementary experimental systems and  further push forward novel technologies such as high-resolution TCR  repertoire analysis, high-dimensional phenotypic analysis by  multi-parameter and mass cytometry and single cell RNA sequencing to  understand how the γδ TCR receives and transduces external signals.
On  the long run, the overarching goals of FOR 2799 will be i) to increase  the visibility of German γδ T cell research, ii) to identify how γδ T  cells respond to neoplastic and infected cells and iii) to explore how  our knowledge on γδ T cell activation can be translated into clinical  strategies for their in vivo manipulation, e.g. in anti-tumor therapy.