title: MOG transmembrane and cytoplasmic domains contain highly stimulatory T-cell epitopes in MS.
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.
authors.affiliation: Department of Neurology and Program in Immunology (M.V.-D., A.S., C.M.S., U.S.-T., B.A.C.C., S.S.Z.), University of California, San Francisco; Department of Neuropathology and Department of Neurology (M.S.W.), University Medical Center, Georg-August University, Göttingen, Germany; Multiple Sclerosis Research Group (C.C.A.B.), Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia; Department of Immunology (T.F.), University of Texas at San Antonio; and Boehringer Ingelheim (A.J.S.), Ridgefield, CT.
authors.forename: Michel
authors.initials: M
authors.lastname: Varrin-Doyer
authors.affiliation: Department of Neurology and Program in Immunology (M.V.-D., A.S., C.M.S., U.S.-T., B.A.C.C., S.S.Z.), University of California, San Francisco; Department of Neuropathology and Department of Neurology (M.S.W.), University Medical Center, Georg-August University, Göttingen, Germany; Multiple Sclerosis Research Group (C.C.A.B.), Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia; Department of Immunology (T.F.), University of Texas at San Antonio; and Boehringer Ingelheim (A.J.S.), Ridgefield, CT.
authors.forename: Aparna
authors.initials: A
authors.lastname: Shetty
authors.affiliation: Department of Neurology and Program in Immunology (M.V.-D., A.S., C.M.S., U.S.-T., B.A.C.C., S.S.Z.), University of California, San Francisco; Department of Neuropathology and Department of Neurology (M.S.W.), University Medical Center, Georg-August University, Göttingen, Germany; Multiple Sclerosis Research Group (C.C.A.B.), Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia; Department of Immunology (T.F.), University of Texas at San Antonio; and Boehringer Ingelheim (A.J.S.), Ridgefield, CT.
authors.forename: Collin M
authors.initials: CM
authors.lastname: Spencer
authors.affiliation: Department of Neurology and Program in Immunology (M.V.-D., A.S., C.M.S., U.S.-T., B.A.C.C., S.S.Z.), University of California, San Francisco; Department of Neuropathology and Department of Neurology (M.S.W.), University Medical Center, Georg-August University, Göttingen, Germany; Multiple Sclerosis Research Group (C.C.A.B.), Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia; Department of Immunology (T.F.), University of Texas at San Antonio; and Boehringer Ingelheim (A.J.S.), Ridgefield, CT.
authors.forename: Ulf
authors.initials: U
authors.lastname: Schulze-Topphoff
authors.affiliation: Department of Neurology and Program in Immunology (M.V.-D., A.S., C.M.S., U.S.-T., B.A.C.C., S.S.Z.), University of California, San Francisco; Department of Neuropathology and Department of Neurology (M.S.W.), University Medical Center, Georg-August University, Göttingen, Germany; Multiple Sclerosis Research Group (C.C.A.B.), Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia; Department of Immunology (T.F.), University of Texas at San Antonio; and Boehringer Ingelheim (A.J.S.), Ridgefield, CT.
authors.forename: Martin S
authors.initials: MS
authors.lastname: Weber
authors.affiliation: Department of Neurology and Program in Immunology (M.V.-D., A.S., C.M.S., U.S.-T., B.A.C.C., S.S.Z.), University of California, San Francisco; Department of Neuropathology and Department of Neurology (M.S.W.), University Medical Center, Georg-August University, Göttingen, Germany; Multiple Sclerosis Research Group (C.C.A.B.), Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia; Department of Immunology (T.F.), University of Texas at San Antonio; and Boehringer Ingelheim (A.J.S.), Ridgefield, CT.
authors.forename: Claude C A
authors.initials: CC
authors.lastname: Bernard
authors.affiliation: Department of Neurology and Program in Immunology (M.V.-D., A.S., C.M.S., U.S.-T., B.A.C.C., S.S.Z.), University of California, San Francisco; Department of Neuropathology and Department of Neurology (M.S.W.), University Medical Center, Georg-August University, Göttingen, Germany; Multiple Sclerosis Research Group (C.C.A.B.), Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia; Department of Immunology (T.F.), University of Texas at San Antonio; and Boehringer Ingelheim (A.J.S.), Ridgefield, CT.
authors.forename: Thomas
authors.initials: T
authors.lastname: Forsthuber
authors.affiliation: Department of Neurology and Program in Immunology (M.V.-D., A.S., C.M.S., U.S.-T., B.A.C.C., S.S.Z.), University of California, San Francisco; Department of Neuropathology and Department of Neurology (M.S.W.), University Medical Center, Georg-August University, Göttingen, Germany; Multiple Sclerosis Research Group (C.C.A.B.), Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia; Department of Immunology (T.F.), University of Texas at San Antonio; and Boehringer Ingelheim (A.J.S.), Ridgefield, CT.
authors.forename: Bruce A C
authors.initials: BA
authors.lastname: Cree
authors.affiliation: Department of Neurology and Program in Immunology (M.V.-D., A.S., C.M.S., U.S.-T., B.A.C.C., S.S.Z.), University of California, San Francisco; Department of Neuropathology and Department of Neurology (M.S.W.), University Medical Center, Georg-August University, Göttingen, Germany; Multiple Sclerosis Research Group (C.C.A.B.), Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia; Department of Immunology (T.F.), University of Texas at San Antonio; and Boehringer Ingelheim (A.J.S.), Ridgefield, CT.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Slavin
authors.affiliation: Department of Neurology and Program in Immunology (M.V.-D., A.S., C.M.S., U.S.-T., B.A.C.C., S.S.Z.), University of California, San Francisco; Department of Neuropathology and Department of Neurology (M.S.W.), University Medical Center, Georg-August University, Göttingen, Germany; Multiple Sclerosis Research Group (C.C.A.B.), Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia; Department of Immunology (T.F.), University of Texas at San Antonio; and Boehringer Ingelheim (A.J.S.), Ridgefield, CT.
authors.forename: Scott S
authors.initials: SS
authors.lastname: Zamvil