Unsere Projekte

 

Antigens of disease related T cells

We are investigating the so far elusive target antigens of tissue-invasive T cells from brain lesions of MS patients, from patients with paraneoplastic neurological diseases, from skin of patients with psoriasis, and from other disease conditions. Over the last years we have established several techniques that now allow us to identify the target antigens of CD8+ T cells. We have established criteria to distinguish putatively autoaggressive T cells from irrelevant cells. Then we isolate single putatively disease-related T cells from biopsy samples, clone their T cell receptor (TCR) α- and β-chains, and functionally express the TCRs in vitro. Most recently, we have developed a new, unbiased technology to identify their as yet unknown antigens. This method is based on plasmid-coded combinatorial peptide libraries which can be loaded onto class I MHC molecules. Further, we have developed a new, extremely sensitive screening system which allows testing of many millions of library compounds within a few hours.

Although our major interest regards research on MS and related diseases, our new technology may be applied to all conditions where CD8+ T cells are relevant, i.e. to many autoimmune, tumor and infectious diseases. Our approach differs from previous studies in that our unbiased strategy is designed for discovering novel antigens rather than merely testing previously known “candidate antigens”. Depending on the progress and specific results, we therefore anticipate entering uncharted territory. We expect to find similar antigens of different CD8+ T cells from different patients.  This may shed light on one of the most fundamental aspect of the pathogeneses of the respective disease.

Antigens of oligoclonal band antibodies

OCB antibodies were described decades ago and are diagnostic hallmarks of MS, but so far their target antigens have remained elusive. We could formally show that OCBs may be produced by CSF-resident B-cells and that the antibody repertoires in the brain parenchyma and the CSF overlap. Based on these studies, we have recently developed a new protein-based method that allows us to identify matching heavy and light chains from individual OCBs and to express recombinant antibodies (rAb) that represent distinct OCB antibodies. We are planning to produce a panel of such rAb from different patients and to use them for antigen-search experiments. Identification of their antigens by classical biochemical tools will be a first step to understand the functional role of OCBs in MS.

 
EN

Direktion

Prof. Dr.

Reinhard Hohlfeld

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Prof. Dr.

Martin Kerschensteiner

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Gruppenleiter

PD. Dr.

Klaus Dornmair

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