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The search for the target antigens of multiple sclerosis, part 2: CD8+ T cells, B cells, and antibodies in the focus of reverse-translational research

Reinhard Hohlfeld, Klaus Dornmair, Edgar Meinl, Hartmut Wekerle

The Lancet Neurology, Volume 15, Issue 3, March 2016, Pages 317–331

Summary

Interest in CD8+ T cells and B cells was initially inspired by observations in multiple sclerosis rather than in animal models: CD8+ T cells predominate in multiple sclerosis lesions, oligoclonal immunoglobulin bands in CSF have long been recognised as diagnostic and prognostic markers, and anti-B-cell therapies showed considerable efficacy in multiple sclerosis. Taking a reverse-translational approach, findings from human T-cell receptor (TCR) and B-cell receptor (BCR) repertoire studies provided strong evidence for antigen-driven clonal expansion in the brain and CSF. New methods allow the reconstruction of human TCRs and antibodies from tissue-infiltrating immune cells, which can be used for the unbiased screening of antigen libraries. Myelin oligodendrocyte glycoprotein (MOG) has received renewed attention as an antibody target in childhood multiple sclerosis and in a small subgroup of adult patients with multiple sclerosis. Furthermore, there is growing evidence that a separate condition in adults exists, tentatively called MOG-antibody-associated encephalomyelitis, which has clinical features that overlap with neuromyelitis optica spectrum disorder and multiple sclerosis. Although CD8+ T cells and B cells are thought to have a pathogenic role in some subgroups of patients, their target antigens have yet to be identified.


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About the Editors

  • Prof Timothy Vartanian

    Timothy Vartanian, Professor at the Brain and Mind Research Institute and the Department of Neurology, Weill Cornell Medical College, Cornell...
  • Dr Claire S. Riley

    Claire S. Riley, MD is an assistant attending neurologist and assistant professor of neurology in the Neurological Institute, Columbia University,...
  • Dr Rebecca Farber

    Rebecca Farber, MD is an attending neurologist and assistant professor of neurology at the Neurological Institute, Columbia University, in New...

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Note that EMD Serono, Inc., has no editorial control or influence over the content of this Resource Centre. The Resource Centre and all content therein are subject to an independent editorial review.

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