Nikolaj Pagh Kristensen
Proteome-wide mapping of T-cell specificity in multiple sclerosis
Nikolaj Pagh Kristensen, Health Tech at the Technical University of Copenhagen, has received a Lundbeck Foundation Postdoc grant worth DKK 2,420,000.
About the project
Immune responses towards self-proteins (i.e. autoantigens) can lead to autoimmune disease. This is true for animal models of multiple sclerosis (MS), but strong evidence supporting that single autoantigens drive neuroinflammation in MS patients remains circumstantial. Combining state-of-the-art single-cell sequencing (scSeq) with CRISPR/Cas9-mediated orthotopic T cell receptor (TCR) replacement as well as a genome-wide epitope discovery platform, Nikolaj Pagh Kristensen seeks to reveal novel autoantigens for CD4 and CD8 T cells and resolve phenotypic heterogeneity of autoantigen-specific T cells in the cerebrospinal fluid of MS patients leading to targetable protein markers for further research and drug development.
To this end, he will perform scSeq of T cells infiltrating the cerebrospinal fluid (CSF) of MS patients. Identified TCRs expressed in primary human T cells will be used as input for mapping of proteome-wide autoreactivity together with reporter cells presenting one of 200.000 autoantigens.
Finally, the project will pair autoantigen and TCR data to augmentthe scSeq dataset recorded for the initial CSF samples to define marker genes that identify autoantigen-specific CD4 and CD8 T cells in the CSF of MS pathology.
Overall, the LF Postdoc project will provide unique insights into MS immunopathology and thereby define a new frontier for MS research and drug development.
