Assoziierter Professor für Immunologie
Medizinische Universität Wien
Abteilung Immunzellen Rezeptoren und Aktivierung der T-Zellen
Institut für Immunologie
Zentrum für Pathophysiologie, Infektiologie und Immunologie
Lazarettgasse 19, 3. Stock
1090 Wien
Tel.: +43 (0)1 40160 - 33241
Fax: +43 (0)1 40160 - 933201
E-Mail: peter.steinberger@meduniwien.ac.at
Research Interests
T cell activation, Costimulation, Regulation of T cell Responses Receptor-Ligand-Interaction.
Immunity is regulated by a complex network of receptor ligand interactions. Our team wants to dissect how signals generated upon interaction of individual surface receptors expressed on immune cells with their cognate ligands impact on immune responses. We believe that it is important to study mechanisms of human immune responses to understand protective immunity but also pathological processes that threaten our health.
Consequently our research focuses on in vitro studies with human immune cells. A major part of our work deals with costimulatory and coinhibitory pathways that promote or inhibit T cell responses, respectively. We study their role in regulating human T cell responses to allergens, viruses and tumours. In our newly established Christian Doppler Laboratory for Complement Research we are investigating the role of novel complement receptors in regulating innate and adaptive immune responses. We are developing and using molecular and cellular tools that help us to address the role of individual receptor-ligand interactions during immune responses.
Our tools
A strong emphasis of our work is on engineering molecular and cellular tools that allow us to assess the impact of individual receptor-ligand interaction on the activation and response of immune cells.
We have devised and widely used a system of T cell stimulator cells (TCS) that can be used to analyse the role of individual costimulatory and coinhibitory molecules in T cell activation processes. A focus of our current research is to render this system antigen-specific. We will use such antigen-specific T cell stimulator cells to identify exogenous signals that strengthen “good or productive T cell responses” – directed towards pathogen and tumour antigens - but also to find pathways that have the potential to abate or redirect pathological T cell responses e.g. Th2-T cells that recognize allergens.
We have recently developed a reliable suite of T cell transcriptional reporter cells to study the function of accessory receptors in a reductionist model of human T cell activation. Our system is based on fluorescent protein readout for high-throughput analysis by flow-cytometry. Used together with our TCS cells, our reporters are a useful tool to investigate various aspects of T cell activation. We are currently using this system to study the function of emerging coinhibitory receptors. By introducing mutations we dissect how the cytoplasmic domains of receptors communicate with the intracellular signalling machinery. Moreover we use these cells to identify and validate potent blocking or agonistic agents (e.g. antibodies to checkpoint inhibitors), which are subsequently used in more complex cellular assays with primary T cells.
A major goal of our work is to identify novel receptor-ligand interactions and to study their contribution to immune responses. We have generated comprehensive eukaryotic expression cDNA libraries from human dendritic cells (DC) as well as from resting and activated human mononuclear cells (MNC). We have expressed these libraries in various human and non-human cell lines and use recombinant proteins, like immunoglobulin fusion proteins, representing molecules of interest to screen our libraries to identify binding partners for orphan ligands and receptors.
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