Berlin, 02.09. 2024
Max Delbrück Centre and German Cancer Consortium support appointment
On 1 September, Prof. Johannes Huppa took over the Professorship of Tumour Immunology at Charité – Universitätsmedizin Berlin and the associated position of Head of the Institute of Immunology at the Berlin Buch campus. He will conduct research at the Max Delbrück Centre and in the German Consortium for Translational Cancer Research (DKTK). The renowned expert in T-cell recognition wants to elucidate the mechanisms of immunological differentiation between foreign and self in detail in order to improve the treatment of cancer and autoimmune diseases.
What is foreign and what is the body’s own? The central sensor of the immune system that makes this distinction is the so-called T-cell receptor. Johannes Huppa, who worked at various US institutions and most recently at the Medical University of Vienna before moving to Charité, has been studying the molecule and how it works for over 25 years. He has significantly expanded our understanding of the molecular processes surrounding the receptor, particularly with the help of innovative microscopy techniques. Johannes Huppa is now taking over from Prof Thomas Blankenstein, who headed the Institute of Immunology at Charité until the end of 2020. His research group will be based at the Max Delbrück Centre in Berlin Buch, where he will have an affiliation as a translational guest group. His work will also be funded by the DKTK.
T cell receptors sit like antennae on T cells, which, as part of the acquired immune response, constantly patrol the blood, tissue and organs like a patrol commando. If the feelers recognise fragments presented to them by other cells as foreign, they trigger immune reactions – the intruders are eliminated. If the T-cell receptors instead recognise the presented fragments as the body’s own, they remain silent. ‘The distinction between foreign and self is made with astonishing precision and is also extremely sensitive,’ explains Johannes Huppa. ‘A patrolling cell can use its T-cell receptors to detect a single foreign fragment on the surface of an infected somatic cell, which is hidden among thousands of fairly similar but endogenous fragments.’
Tracking down foreign self-recognition with new ‘magnifying glasses’
Just how important this recognition mechanism is for health becomes clear when it does not work perfectly or is faulty: If the differentiation between friend and foe does not work, the body inadvertently turns its immune system against itself, for example, resulting in an autoimmune disease such as multiple sclerosis or type 1 diabetes. Or the immune system fails to recognise malignant tumour cells, which can then become a deadly danger. Increased infections can also occur.
Johannes Huppa wants to find out how exactly a T cell receptor binds to different fragments and which signals it transmits within the T cell, which then decide between foreign and self. To this end, he has developed new microscopy methods with which he can observe living T cells at work. The technique visualises individual receptor molecules on the cell surface, the fragments presented and also the molecular bonds between them. This allows the tiniest mechanical forces to be measured in real time and the activation processes within the T cell to be observed. In Berlin, he will combine these methods with methods of synthetic biology and structural biology approaches in order to elucidate the molecular processes of fragment recognition in terms of time and space at the highest resolution, i.e. on a millisecond and nanometre scale.
Influencing T-cell receptors to treat cancer and autoimmune diseases
The immunologist’s aim is to find ways to intervene in the function of the T-cell receptor. This should make anti-cancer therapies in particular more effective. ‘If we understand exactly how the T-cell receptor achieves its immunological feat, we can better exploit the potential of novel immunotherapies such as CAR-T and TCR-T cell therapy,’ explains the new Institute Director. He would also like to use the knowledge to advance the development of new vaccines against cancer and to switch off harmful T cells in autoimmune diseases or rejection reactions following an organ transplant.
‘Collaboration with our clinical colleagues at the Charité is essential for this,’ emphasises Johannes Huppa. ‘The close proximity to the experts in structural biology and tumour immunology at the Max Delbrück Center and the outstanding technological infrastructure on the Berlin Buch campus will also be crucial to achieving these goals. The Berlin site is known beyond Germany’s borders for its strength, versatility and collegiality in basic and clinical research. I am delighted to now be part of this great network.’
Short biography
Johannes Huppa (*12 May 1967 in Thuine, Emslandkeis) studied biochemistry at the Free University of Berlin and researched T-cell receptors in his diploma thesis at the Massachusetts Institute of Technology (MIT) in Cambridge, USA. He continued these studies as part of his doctoral thesis at MIT and Harvard Medical School, for which he received his doctorate from the Vrije Universiteit Amsterdam in 1998. He conducted research at Standford University School of Medicine in the San Francisco Bay Area, first as a postdoctoral researcher and then as a Basic Science Research Associate, before being appointed to an assistant professorship at the Medical University of Vienna in 2012. From 2015, he headed the Immune Recognition Research Group at the Centre for Pathophysiology, Infectiology and Immunology as an Associate Professor.