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

@article{Planas2018GDPlfucoseSI,
  title={GDP-l-fucose synthase is a CD4+ T cell–specific autoantigen in DRB3*02:02 patients with multiple sclerosis},
  author={Raquel Planas and Radleigh G Santos and Paula Tomas-Ojer and Carolina Cruciani and Andreas Lutterotti and Wolfgang Faigle and Nicole Schaeren-Wiemers and Carmen Espejo and Herena Eixarch and Clemencia Pinilla and Roland Martin and Mireia Sospedra},
  journal={Science Translational Medicine},
  year={2018},
  volume={10}
}
GDP-l-fucose synthase is an autoantigen recognized by cerebrospinal fluid–infiltrating CD4+ T cells from HLA-DRB3* patients with multiple sclerosis. Move over myelin Although it is well established that autoreactive lymphocytes induce demyelination in multiple sclerosis, the exact antigenic targets that initiate disease are undefined. Planas et al. studied CD4+ T cells from the cerebrospinal fluid of patients with multiple sclerosis. One CD4+ T cell clone was reactive to the human enzyme GDP-l… Expand
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References

SHOWING 1-10 OF 94 REFERENCES
HLA DRB4 0101-restricted immunodominant T cell autoepitope of pyruvate dehydrogenase complex in primary biliary cirrhosis: evidence of molecular mimicry in human autoimmune diseases
TLDR
Six T cell clones specific for pyruvate dehydrogenase complex (PDC)-E2 peptides from four different patients with primary biliary cirrhosis are established using 33 different peptides of 17-20 amino acid residues corresponding to human PDC-E2 as stimulating antigens, demonstrating the presence of molecular mimicry at the T cell clonal level in human autoimmune diseases. Expand
A myelin basic protein peptide is recognized by cytotoxic T cells in the context of four HLA-DR types associated with multiple sclerosis
TLDR
The fine specificity of the T cell response to myelin basic protein in patients with multiple sclerosis and healthy controls is studied using four well-characterized, monospecific T cell lines from three MS patients and an identical twin of a patient to study the response to this region of the MBP molecule. Expand
T-cell recognition of an immuno-dominant myelin basic protein epitope in multiple sclerosis
TLDR
A higher frequency of T-cell lines reactive with a DR2-associated region of myelin basic protein between residues 84–102 in patients with multiple sclerosis compared with controls is reported, raising the possibility that this immunodominant region may be encephalitogenic in some DR2+ individuals. Expand
Fine specificity and HLA restriction of myelin basic protein-specific cytotoxic T cell lines from multiple sclerosis patients and healthy individuals.
TLDR
The findings suggest that the MBP-specific cytotoxic T cell response, although not sufficient for disease, may be important for the pathogenesis of MS. Expand
Expansion and Functional Relevance of High-Avidity Myelin-Specific CD4+ T Cells in Multiple Sclerosis
TLDR
Correlations between selected immunological parameters and magnetic resonance imaging markers indicate that the specificity and function of these cells influences phenotypic disease expression. Expand
GM-CSF Production Allows the Identification of Immunoprevalent Antigens Recognized by Human CD4+ T Cells Following Smallpox Vaccination
TLDR
A “T cell–driven” methodology that can be implemented to determine the specificity of the T cell response upon vaccination or infection is described, and clear evidence that TNF-α is an excellent readout of vaccinia specificity is presented. Expand
A Gut Microbial Mimic that Hijacks Diabetogenic Autoreactivity to Suppress Colitis
TLDR
The data suggest that gut microbial antigen-specific cytotoxic T cells may have therapeutic value in inflammatory bowel disease and unearth molecular mimicry as a novel mechanism by which the gut microbiota can regulate normal immune homeostasis. Expand
The search for the target antigens of multiple sclerosis, part 1: autoreactive CD4+ T lymphocytes as pathogenic effectors and therapeutic targets
TLDR
One major obstacle to personalised, highly selective immunotherapy is the absence of standardised and reliable assays to assess antigen-specific human T-cell responses, which would be essential for stratification of patients with multiple sclerosis according to their individual target antigens. Expand
Myelin basic protein‐specific T lymphocyte lines from MS patients and healthy individuals
TLDR
Findings illustrate the presence of MBP-specific T cells in MS patients and controls that are similarly sensitized to MBP and restricted by HLA-DR products. Expand
RORγt drives production of the cytokine GM-CSF in helper T cells, which is essential for the effector phase of autoimmune neuroinflammation
TLDR
It is reported that interleukin 23 and the transcription factor RORγt drove expression of the cytokine GM-CSF in helper T cells, whereas IL-12, interferon-γ (IFN-γ) and IL-27 acted as negative regulators. Expand
...
1
2
3
4
5
...