Whether a killer T cell in our immune system protects or harms us depends on which antigen it binds to with its typical receptor. However, it is largely unknown which antigens these receptors recognize, especially in cancer and autoimmune diseases, but also in many infections. PD Dr. Kilian Schober and his research group at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) are working to shed light on this darkness - and have now been awarded a Life Sciences Bridge Award worth 100,000 euros by the Aventis Foundation.
The T cells of our adaptive immune system protect us from infections and cancer, but can also turn against our own body and cause autoimmune diseases. Whether they help or harm us depends on which antigens, small peptides, they bind to in order to trigger an immune response.
On their patrols through the body, every cytotoxic T cell mainly encounters self-peptides from healthy cells - and must find the foreign antigen that matches its specific receptor in the midst of these so that it does not inadvertently destroy healthy cells.
“It is a largely unsolved question which epitopes T cells actually recognize as antigens and how this antigen specificity of their receptors influences the T cell response,” says Kilian Schober, who heads the research group ‘Understanding & Engineering Human T Cell Immunity’ at the Institute of Microbiology - Clinical Microbiology, Immunology and Hygiene at FAU's University Hospital Erlangen, explaining his research interest. This applies not only to cancer and autoimmune diseases, but also to many infectious diseases.
The best model is the vaccination against yellow fever, which provides lifelong protection and is therefore considered a blueprint for a successful immune response. As one of the research group leaders of an EU-Horizon joint project, Schober has been using this blueprint since January 2024 to analyze immune responses to West Nile and Zika viruses, among others, which are already present or will arrive in Europe as a result of climate change. Where possible, Schober transfers what he learns from vaccination models to other disease models.
To this end, the researcher uses two technologies that allow him to advance into new dimensions of understanding T cell responses: genome editing using CRISPR/Cas and single-cell RNA sequencing. With the latter, he can sequence all the active genes of a single T cell, including those of its receptor, and make precise genetic modifications to the receptor. In this way, a library of T cell receptors including validated epitopes is built up in order to find the epitopes that match the T cell receptor.
“Understanding T cell responses at the molecular level is of eminent importance for the development of effective immunotherapies. Kilian Schober is a pioneer in this field,” says Prof. Dr. Werner Müller-Esterl, Chairman of the Life Sciences Bridge Award jury. “With this award, we would like to help him cross the bridge to a permanent professorship.”
The Life Sciences Bridge Award is one of the most highly endowed prizes for young scientists in Germany, awarded by the Aventis Foundation, an independent, non-profit foundation for the promotion of art and culture as well as science, research and teaching based in Frankfurt am Main.