Scientific Scope

Our research explores how the adaptive and innate branches of the immune system act in concert to differentiate healthy from abnormal and friend from foe. We focus on three core questions:

• How do T-cells recognize antigens at cellular, subcellular, and molecular scales?

• What degree of cross-reactivity do T-cells exhibit when scanning a plethora of different antigens, and how does T-cell cross-reactivity influence immunity in cancer and autoimmunity?

• How do antigen-presenting or target cells modulate T-cell antigen recognition?

Using a combination of cell biological, biophysical, and genetic approaches, we aim for quantitative answers. Our goal is to understand how T-cells achieve their remarkable antigen selectivity and sensitivity, while maintaining a delicate balance between tolerance and immunity. We strive to harness these insights to advance T-cell-based precision medicine in cancer and autoimmune diseases.

To achieve this, we engineer and utilize fluorescent probes and protein-functionalized planar supported lipid bilayers, enabling real-time observation of primary T-cells at work via advanced single-molecule live-cell imaging techniques. Moving forward, we aspire to integrate structural biology for enhanced spatial resolution, alongside bioinformatics and machine learning, to better capture the complexities of membrane biophysics and systems biomedicine associated with T-cell antigen recognition.

Most important Awards, Grants or Scientific Achievements

2024                   Emerging Fields Excellence Initiative of the Austrian Government, excellent = Austria
2013, 2014       Vienna Science and Technology Fund
2020                   Guy Newton Sabbatical Fellowship, Oxford University
2007                   Fellowship, iFREC (Immunology Frontiers Research Center) imaging consortium, Japan 
1999                   Cancer Research Institute, USA (fellowship, 1999 - also accepted for funding by the Irvington and the                               Arthritis Foundation) 
1994                   Boehringer Ingelheim Fonds, Germany (fellowship PhD thesis)          
1993                   Gottlieb Daimler- and Carl Benz-Foundation, Germany (fellowship diploma thesis)    

 

 

Group Members

Janett Göhring, PhD, Postdoc

Stefan Stoiber PhD, Postdoc

Johannes Holler, MSc., PhD student

Vanessa Mühlgrabner, MSc., PhD student

Nataliia Novikova, MSc., PhD student

Christian Friese, Technician

Christina Möwes, Technician

Selected References

• Mühlgrabner. V., Peters, T., Velasco Cárdenas, R.M.H., Salzer, B., Göhring, J., Plach, A., Höhrhan, M., Doel Perez, I., Dos Reis Gonçalves, V., Siller-Farfán, J., Lehner, M., Stockinger, H., Schamel, W.W., Schober, K., Busch, D.H., Hudecek, M., Dushek, O., Minguet, S., Platzer, R, Huppa, J.B. (2024) "TCR/CD3-based synthetic antigen receptors (TCC) convey superior antigen sensitivity combined with high fidelity of activation." Science Advances 10(36):eadj4632. doi: 10.1126/sciadv.adj4632
• Platzer, R., Hellmeier, J., Göhring, J., Doel-Perez, I., Schatzlmaier, P., Bodner, C., Schütz, G.J., Sevcsik, E., Stockinger, H., Brameshuber, H., Huppa, J.B. (2023) "Monomeric agonist peptide/MHCII complexes activate T-cells in an autonomous fashion." EMBO Reports Sep 28:e57842. doi: 10.15252/embr.202357842
• Göhring, J., Kellner, F., Schrangl, L., Platzer, R., Klotzsch, E., Stockinger, H., Huppa, J.B., Schütz, G.J. (2021) "Temporal Analysis of T-Cell Receptor-Imposed Forces via Quantitative Single Molecule FRET Measurements." Nature Communications  4;12(1):2502. doi: 10.1038/s41467-021-22775-z. PMID: 33947864.
• Gudipati, V., Rydzek, J., Doel Perez, I., Scharf, L., Königsberger, S., Lobner, E., Dos Reis Gonçalves, V., Kunert, R., Einsele, H., Stockinger, H., Hudecek, M. and Huppa, J.B. (2020) "Inefficient CAR-proximal signaling blunts antigen detection."  Nature Immunology 21:848-856 doi: 10.1038/s41590-020-0719-0. online ahead of print. PMID: 32632291
• Brameshuber, M., Kellner, F., Rossboth, B.K., Ta, H., Alge, K., Sevcsik, E., Göhring, J., Axmann, M., Baumgart, F., Gascoigne, N.R.J., Davis, S.J., Stockinger, H., Schütz, G.J. Huppa, J.B.* (2018) "Monomeric TCRs Drive T-Cell Antigen Recognition." Nature Immunology, 19(5):487-496, doi: 10.1038/s41590-018-0092-4