Deep Sequencing of myelin-reactive T-cells to elucidate new disease mechanisms and identify correlates for treatment responsiveness.

Whereas antigen-specific activation of autoreactive T-cells is considered essential in the initiation and maintenance of MS, how to identify the broad repertoire of unique receptors expressed by these autoreactive T-cells from blood remains unclear. Nonetheless, with improved T-cell receptor (TCR)-sequencing technological development, efforts in identifying immune T-cell signatures in blood, CSF and brain lesions of MS patients have been initiated. Although accurately evaluating TCR clonal expansion using high throughput sequencing in bulk DNA/RNA has been challenging, single-cell sequencing allows to establish TCR repertoires of autoreactive T-cells on a cell-by-cell basis, obtain full-length V(D)J sequences, pair α and β sequences and combine TCR with 5' transcriptome sequencing in the same cells, and this for 1000s of cells. The combined expertise of our interuniversity team in immunology and characterization of autoreactive T-cells (N. Cools, U Antwerp) on the one hand and in genetics and single-cell sequencing (A. Goris, KU Leuven) on the other makes it now feasible, timely and innovative to investigate the pathogenic characteristics of autoreactive T-cells in MS. For this, the following three aims have been set forth: 1. What is the TCR repertoire of autoreactive T-cells in MS? 2. What are the transcriptional characteristics of autoreactive T-cells? 3. Can the autoreactive T-cell clonotype repertoire be used as a correlate for therapy responsiveness?

Keywords:T CELL SUBSETS, TCR SEQUENCING, MULTIPLE SCLEROSIS

Disciplines:Cell, tissue and organ engineering, DNA analysis technology, Autoimmunity

Project type:Collaboration project