RT Journal Article
SR Electronic
T1 MOG transmembrane and cytoplasmic domains contain highly stimulatory T-cell epitopes in MS
JF Neurology - Neuroimmunology Neuroinflammation
JO Neurol Neuroimmunol Neuroinflamm
FD Lippincott Williams & Wilkins
SP e20
DO 10.1212/NXI.0000000000000020
VO 1
IS 2
A1 Varrin-Doyer, Michel
A1 Shetty, Aparna
A1 Spencer, Collin M.
A1 Schulze-Topphoff, Ulf
A1 Weber, Martin S.
A1 Bernard, Claude C.A.
A1 Forsthuber, Thomas
A1 Cree, Bruce A.C.
A1 Slavin, Anthony J.
A1 Zamvil, Scott S.
YR 2014
UL http://nn.neurology.org/content/1/2/e20.abstract
AB 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.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