FocusMultiple Sclerosis

T cells take aim at a ubiquitous autoantigen in multiple sclerosis

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Science Translational Medicine  10 Oct 2018:
Vol. 10, Issue 462, eaau8826
DOI: 10.1126/scitranslmed.aau8826


  • Fig. 1 Possible mechanisms for expansion of GDP-l-fucose synthase–reactive CD4+ T cells in MS.

    More than one model can explain how GDP-l-fucose synthase–reactive CD4+ T cells participate in CNS inflammation. In the cross-reactivity model (left), GDP-l-fucose synthase protein is expressed by commensal bacteria, perhaps by species overrepresented in the gastrointestinal tract of patients with MS. These peptides are presented by local APCs, thereby activating CD4+ T cells that cross-react with human GDP-l-fucose synthase. Activated GDP-l-fucose–reactive T cells can migrate to the CNS, where they may contribute to MS pathology, either by (i) direct cross-reactivity to pathogenic determinants of myelin antigens or (ii) acting synergistically with CD4+ T cells specific for myelin. In the model of epitope spreading (right), myelin-reactive CD4+ T cells traffic from the periphery to the CNS and initiate inflammation and demyelination. Cellular debris, including ubiquitous self-antigens, is released and processed by local APCs, leading to a secondary activation and expansion of GDP-l-fucose synthase–reactive CD4+ T cells. Currently, whether GDP-l-fucose synthase–specific T cells are inert (i.e., bystander), suppress or propagate CNS inflammation is unknown.


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