Adaptive Immunity; Autoimmunity; Biophysics; Cell Biology; Microscopy
In the Huppa lab we are interested in how the adaptive and innate branch of the immune system work together to distinguish between friend and foe. For the most part our curiosity revolves around two questions:
- How do lymphocytes, in particular T cells, recognize antigens on a molecular, subcellular and cellular level?
- How do Antigen Presenting Cells modulate antigen-specific T cell responses?
We are aiming for quantitative answers by cell biological, biophysical and genetic means to explain how T cells establish their exquisite antigen selectivity and sensitivity and maintain the right balance between tolerance and immunity. Furthermore, we are investigating the molecular mechanisms underlying tumor recognition by Chimeric Antigen Receptor modified T cells (CAR T cells), as a means to optimize CAR T cell performance in cancer immunotherapy.
Techniques, methods & infrastructure
To this end we engineer fluorescent probes and functionalized lipid bilayers, which we employ to study primary T cells and APCs in innovative laser microscopy experiments. We complement microscopy with state of the art methods in immunology and molecular biology to monitor and manipulate gene expression and immune function.
- Brameshuber, M. et al. (2018) ‘Monomeric TCRs drive T cell antigen recognition’, Nature Immunology, 19(5), pp. 487–496. Available at: http://dx.doi.org/10.1038/s41590-018-0092-4.
- Rossboth, B. et al. (2018) ‘TCRs are randomly distributed on the plasma membrane of resting antigen-experienced T cells’, Nature Immunology, 19(8), pp. 821–827. Available at: http://dx.doi.org/10.1038/s41590-018-0162-7.
- Axmann, M., Schütz, G.J. and Huppa, J.B. (2015) ‘Measuring TCR-pMHC Binding <em>In Situ</em> using a FRET-based Microscopy Assay’, Journal of Visualized Experiments [Preprint], (104). Available at: http://dx.doi.org/10.3791/53157.
- Huppa, J.B. and Davis, M.M. (2013) ‘The Interdisciplinary Science of T-cell Recognition’, Advances in Immunology, pp. 1–50. Available at: http://dx.doi.org/10.1016/b978-0-12-407707-2.00001-1.
- Huppa, J.B. et al. (2010) ‘TCR–peptide–MHC interactions in situ show accelerated kinetics and increased affinity’, Nature, 463(7283), pp. 963–967. Available at: http://dx.doi.org/10.1038/nature08746.