Mathematics Faculty Articles

GDP-L-Fucose Synthase is a CD4+ T Cell–Specific Autoantigen in DRB3*02:02 Patients with Multiple Sclerosis

Document Type

Article

Publication Date

10-10-2018

Publication Title

Science Translational Medicine

ISSN

1946-6234

Volume

10

Issue/No.

462

First Page

eaat4301

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.

Comments

©2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works

Additional Comments

DFG Center grant #s: SFB 841, SNF: 310030_146945; European Research Council Advanced Grant #: 340733

DOI

10.1126/scitranslmed.aat4301

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