Format

Send to

Choose Destination
Sci Transl Med. 2018 Oct 10;10(462). pii: eaat4301. doi: 10.1126/scitranslmed.aat4301.

GDP-l-fucose synthase is a CD4+ T cell-specific autoantigen in DRB3*02:02 patients with multiple sclerosis.

Author information

1
Neuroimmunology and MS Research (nims), Department of Neurology, University Hospital Zurich, Frauenklinikstrasse 26, 8091 Zürich, Switzerland.
2
Torrey Pines Institute for Molecular Studies, 11350 SW Village Parkway Port St. Lucie, FL 34987, USA.
3
Department of Biomedicine, University Hospital Basel, Hebelstrasse 20, 4031 Basel, Switzerland.
4
Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya, Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, 08035 Barcelona, Spain.
5
Neuroimmunology and MS Research (nims), Department of Neurology, University Hospital Zurich, Frauenklinikstrasse 26, 8091 Zürich, Switzerland. mireia.sospedraramos@usz.ch.

Abstract

Multiple sclerosis is an immune-mediated autoimmune disease of the central nervous system that develops in genetically susceptible individuals and likely requires environmental triggers. The autoantigens and molecular mimics triggering the autoimmune response in multiple sclerosis remain incompletely understood. By using a brain-infiltrating CD4+ T cell clone that is clonally expanded in multiple sclerosis brain lesions and a systematic approach for the identification of its target antigens, positional scanning peptide libraries in combination with biometrical analysis, we have identified guanosine diphosphate (GDP)-l-fucose synthase as an autoantigen that is recognized by cerebrospinal fluid-infiltrating CD4+ T cells from HLA-DRB3*-positive patients. Significant associations were found between reactivity to GDP-l-fucose synthase peptides and DRB3*02:02 expression, along with reactivity against an immunodominant myelin basic protein peptide. These results, coupled with the cross-recognition of homologous peptides from gut microbiota, suggest a possible role of this antigen as an inducer or driver of pathogenic autoimmune responses in multiple sclerosis.

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center