Defining the Autoimmune Targets of B-cells and T-cells in Multiple Sclerosis

• Applicant: Dr. Tobias Lanz
• Subject Area: Immunology
• Term: from 2014 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 270226177

Autoimmune diseases, including multiple sclerosis (MS), arise from aberrant activation of B- and T-cells to attack self-antigens. Antigen-specific targeting and depletion of autoreactive B- and T-cells would be an optimal treatment for MS and other autoimmune diseases. However, efforts to date have fallen short in part due to an incomplete understanding of the antigen targets of B- and T-lymphocytes in MS and most autoimmune diseases. The goal of this proposal is to identify the antigen targets of the autoimmune B- and T-cells in multiple sclerosis (MS). To elucidate these autoantigen targets, I propose to use a novel technology, called antigen-receptor repertoire capture (ARC), for high-throughput sequence of B and T cell responses, developed in the laboratory of Prof. William H. Robinson at Stanford University. It involves cell-based barcoding of all cDNA from individual B- and T-cells derived from blood, cerebro-spinal fluid and brain tissue of MS patients, followed by deep sequencing of antibody heavy- and light-chains (HC and LC) or T-cell receptor (TCR) alpha- and beta-chains, followed by computational analysis of clonal families of antibodies and TCRs. Predicted pathogenic antibodies and TCRs will be cloned and investigated using peptide arrays and MHC-peptide displays, and MS mouse models used to identify their corresponding antigens and determine their pathogenicity. This research project will pave the way for the development of new biomarkers and antigen-specific treatment strategies for MS.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. William Robinson