Abstract
Objective: Recently, we reported that the 218 amino acid murine full-length myelin oligodendrocyte glycoprotein (MOG) contains novel T-cell epitopes p119-132, p181-195, and p186-200, located within its transmembrane and cytoplasmic domains, and that p119-132 is its immunodominant encephalitogenic T-cell epitope in mice. Here, we investigated whether the corresponding human MOG sequences contain T-cell epitopes in patients with multiple sclerosis (MS) and healthy controls (HC).
Methods: Peripheral blood T cells from patients with MS and HC were examined for proliferation to MOG p119-130, p181-195, p186-200, and p35-55 by fluorescence-activated cell sorting analysis using carboxylfluorescein diacetate succinimidyl ester dilution assay. Intracellular production of proinflammatory cytokines was analyzed by flow cytometry.
Results: MOG p119-130, p181-195, and p186-200 elicited significantly greater T-cell responses than p35-55 in patients with MS. T cells from patients with MS proliferated significantly more strongly to MOG p119-130 and p186-200 than did T cells from HC. Further, MOG p119-130–specific T cells exhibited Th17 polarization, suggesting this T-cell epitope may be relevant to MS pathogenesis.
Conclusions: Transmembrane and cytoplasmic MOG domains contain potent T-cell epitopes in MS. Recognition of these determinants is important when evaluating T-cell responses to MOG in MS and may have implications for development of myelin antigen-based therapeutics.
GLOSSARY
- aa=
- amino acid(s);
- AQP4=
- aquaporin-4;
- CFSE=
- carboxylfluorescein diacetate succinimidyl ester;
- EAE=
- experimental autoimmune encephalitis;
- HC=
- healthy controls;
- Ig=
- immunoglobulin;
- MBP=
- myelin basic protein;
- MHC=
- major histocompatibility complex;
- MOG=
- myelin oligodendrocyte glycoprotein;
- MS=
- multiple sclerosis;
- NMO=
- neuromyelitis optica;
- PLP=
- proteolipid protein;
- PBMC=
- peripheral blood mononuclear cells;
- UCSF=
- University of California at San Francisco
Footnotes
Go to Neurology.org/nn for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. The Article Processing Charge was paid by the authors.
- Received April 30, 2014.
- Accepted in final form July 8, 2014.
- © 2014 American Academy of Neurology
This is an open access article distributed under the terms of the Creative Commons Attribution-Noncommercial No Derivative 3.0 License, which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially.
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