Our research aims to understand

Neuroimmunology
- the development of tissue-specific autoimmunity
- the interaction of the nervous system with the immune system under inflammatory conditions
 
1. Immuno-regulatory properties of central nervous system (CNS)-resident cells in vivo: Specific focus on inflammatory conditions such as multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE)
2. Ag-presentation and processing in the central nervous system
3. Identification of pathogenic molecules specific for autoimmune T lymphocytes
4. The role of innate immunity in the CNS
5. Immune tolerance and lymphoid development
6. Small interfering RNA as a means of gene-suppression of candidate target genes involved in encephalitogenicity.
7. In vivo bioluminescence imaging of signalling events, apoptosis and cell migration
8. The role of humoral immunity in the generation of CNS-inflammation

Viral Immunobiology 
We are interested in the immune control of persistent viral infections. We study the immunobiology of the persistent and oncogenic human gamma-Herpesvirus Epstein Barr virus (EBV). This tumorvirus establishes persistent infection in more than 90% of the human adult population, but only a minority of infected individuals develops spontaneously EBV associated malignancies, like Hodgkin’s disease and nasopharyngeal carcinoma. The importance of EBV specific immune control in healthy virus carriers is documented by the fact that EBV causes B cell lymphomas in immune compromised individuals after hereditary, virus-induced or therapeutical immunosuppression following transplantation.
 
We would like to understand which components of the immune system are essential for this perfect immune control in healthy EBV carriers and how they could be activated for resistance against other persistent infections and against tumors. Four components of EBV specific immune control have been identified. Natural Killer (NK) cells are thought to limit the initial viremia prior to initiation of B and T cell mediated adaptive immunity. Neutralizing antibodies are believed to play a role in controlling lytic EBV infection. During latent and persistent EBV infection EBV specific CD4+ and CD8+ T cell responses shoulder probably most of the burden of preventing EBV associated malignancies.
 
We study currently three main aspects of EBV specific immune control. Our first research area is NK activation and anti-viral NK cell effects especially in secondary lymphoid organs like tonsils, which are the primary site of EBV infection. We have identified a novel NK population in tonsils and lymph nodes as well as documented NK activation by dendritic cells (DCs) as a potential mechanism of the early NK expansion at the onset of immune responses. We are currently investigating the molecular basis of NK activation by DCs, the anti-viral effects of activated NK cells and the role of NK cell activation in shaping the emerging adaptive immune response.
 
Our second research area is tumor recognition by CD4+ T cells. We have characterized the prominent latent EBV antigen for CD4+ T cell recognition, EBNA1, and documented that EBNA1 specific CD4+ T cells recognize EBV positive tumor cells directly. We have identified macroautophagy, a catabolic pathway that delivers cytoplasmic constituents for lysosomal degradation, as the antigen processing pathway that delivers intracellular antigens for MHC class II presentation to CD4+ T cells, and are now  investigating how this pathway is regulated and if it can be used for the improvement of vaccines.
Our third research area is CD4+ T cell dependent CD8+ T cell memory. We have found that dendritic cells cross-present EBV antigens from infected B cells for T cell stimulation and that this pathway is essential for the initiation of EBV specific immune control in vitro. We are now interested if EBV specific CD4+ T cells also modify dendritic cells to maintain long-term EBV specific T cell memory, the hallmark of efficient immune control against persistent Epstein-Barr virus infection.
 
 
Clinical Immunology and Immunotherapy
Our research aims to understand mechanisms leading to neuroinflammatory diseases such as multiple sclerosis (MS) and to develop novel approaches for therapy and prevention.

Areas of interest are:
- Infectious triggers and genetic susceptibility factors in MS
- Innate immune mechanisms in neuroinflammatory diseases
- Antigen recognition in autoimmune tissue inflammation
- Biomarkers for disease classification and treatment response in MS and immune-mediated neuromuscular diseases
- Mechanisms of immunotherapy and development of novel therapeutic strategies to treat neuroinflammatory diseases