The research group focuses on the study of intrathecal immune responses in neurological diseases, in particular multiple sclerosis (MS). Through this, we aim to understand disease mechanisms to contribute to more specific therapeutic approaches.
We have postulated that the immune response in MS is initiated by viruses, such as Epstein Barr virus (EBV), and is driven by T cells and B cells within the central nervous system (CNS). These cells could recognize an exogenous antigen, an autoantigen, or immunogenic determinants, idiotopes (Id), on immunoglobulin (Ig) VH- and VL-fragments expressed by B cells secreting the oligoclonal IgG in the CNS.
To address these questions we study T cells and B cells from the cerebrospinal fluid (CSF) of MS-patients.
From the CSF we have raised several HLA-DR restricted CD4+ T cell lines (TCLs) and clones (TCCs), which recognize autologous monoclonal IgG. The target epitopes were shown to reside on IgG VH- and VL-sequences that contained somatically induced amino acid replacements (i.e. Id).
Moreover, we have shown that Id specific TCCs could induce apoptosis in oligodendrocyte lines, suggesting that Id specific cells can mediate demyelination.
We have also been able to raise EBV specific CD4+ TCLs and TCCs from the CSF of MS patients, and could show that these T cells are inhibited by vitamin D in a dose-dependent fashion.
More recently, we have used high-throughput sequencing to chart the T cell and B cell repertoire in the CSF. This enabled us to characterize the compartmentalization of the B cell and T cell responses within the CSF in great detail. Moreover, we demonstrated that T cell receptors against EBV accumulate in the CSF of MS patients.
The research group employs a wide variety of techniques to map the cellular and humoral immune response in the CSF, such as high-throughput sequencing, flow cytometry, isoelectric focusing, immunoblotting, T cell cloning, and mass spectrometry.
Moreover, in collaboration with researchers in Wisconsin, USA, we use a bioinformatics approach to analyze the B cell Ig VH repertoire and the patterns of T cell exposed amino acid motifs presented on HLA molecules.