2014
Small-Molecule RORγt Antagonists Inhibit T Helper 17 Cell Transcriptional Network by Divergent Mechanisms
Xiao S, Yosef N, Yang J, Wang Y, Zhou L, Zhu C, Wu C, Baloglu E, Schmidt D, Ramesh R, Lobera M, Sundrud MS, Tsai PY, Xiang Z, Wang J, Xu Y, Lin X, Kretschmer K, Rahl PB, Young RA, Zhong Z, Hafler DA, Regev A, Ghosh S, Marson A, Kuchroo VK. Small-Molecule RORγt Antagonists Inhibit T Helper 17 Cell Transcriptional Network by Divergent Mechanisms. Immunity 2014, 40: 477-489. PMID: 24745332, PMCID: PMC4066874, DOI: 10.1016/j.immuni.2014.04.004.Peer-Reviewed Original ResearchMeSH KeywordsAndrostenolsAnimalsBenzeneacetamidesBenzhydryl CompoundsCell DifferentiationCell Line, TumorCell LineageCytokinesDigoxinEncephalomyelitis, Autoimmune, ExperimentalGene Regulatory NetworksHeterocyclic Compounds, 4 or More RingsHumansMiceMice, Inbred C57BLMice, KnockoutMultiple SclerosisMyelin-Oligodendrocyte GlycoproteinNuclear Receptor Subfamily 1, Group F, Member 3Peptide FragmentsProtein BindingStructure-Activity RelationshipSystems BiologyT-Lymphocyte SubsetsTh17 CellsTranscription, GeneticTranscriptional ActivationConceptsTranscriptional networksSignature genesCis-regulatory sitesStrong transcriptional effectsInterconnected regulatory networkCell signature genesSystem-scale analysisTranscriptional regulationDirect repressorTarget lociTranscriptome sequencingRegulatory networksDNA bindingTranscriptional effectsCell lineagesCell differentiationT-cell lineageDirect activatorDivergent mechanismsT cell differentiationSpecific inhibitorDistinct mechanismsPotential therapeutic compoundsGenesRetinoid-related orphan receptor gamma t
2011
Increased Frequencies of Myelin Oligodendrocyte Glycoprotein/MHC Class II-Binding CD4 Cells in Patients with Multiple Sclerosis
Raddassi K, Kent SC, Yang J, Bourcier K, Bradshaw EM, Seyfert-Margolis V, Nepom GT, Kwok WW, Hafler DA. Increased Frequencies of Myelin Oligodendrocyte Glycoprotein/MHC Class II-Binding CD4 Cells in Patients with Multiple Sclerosis. The Journal Of Immunology 2011, 187: 1039-1046. PMID: 21653833, PMCID: PMC3131477, DOI: 10.4049/jimmunol.1001543.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAmino Acid SubstitutionCD4 Lymphocyte CountCD4-Positive T-LymphocytesCell CommunicationCell Line, TransformedCells, CulturedEpitopes, T-LymphocyteFemaleGene FrequencyHLA-DR AntigensHLA-DRB1 ChainsHumansImmunophenotypingMaleMiddle AgedMultiple SclerosisMyelin-Associated GlycoproteinMyelin-Oligodendrocyte GlycoproteinPeptide FragmentsProtein BindingProtein MultimerizationConceptsMyelin-reactive T cellsMultiple sclerosisT cell clonesT cellsHealthy controlsMOG-reactive T cellsAutoantigen-specific T cellsCell clonesStimulation of PMBCsClass II tetramersPathogenic immune cellsReactive T cellsSpecific T cellsMyelin oligodendrocyte glycoproteinHLA class IIBlood of subjectsT-cell cloning techniqueMOG peptidesShort-term cultureCD4 cellsMS subjectsAutoimmune diseasesPeripheral bloodControl subjectsOligodendrocyte glycoprotein
2009
Age-Dependent B Cell Autoimmunity to a Myelin Surface Antigen in Pediatric Multiple Sclerosis
McLaughlin KA, Chitnis T, Newcombe J, Franz B, Kennedy J, McArdel S, Kuhle J, Kappos L, Rostasy K, Pohl D, Gagne D, Ness JM, Tenembaum S, O'Connor KC, Viglietta V, Wong SJ, Tavakoli NP, de Seze J, Idrissova Z, Khoury SJ, Bar-Or A, Hafler DA, Banwell B, Wucherpfennig KW. Age-Dependent B Cell Autoimmunity to a Myelin Surface Antigen in Pediatric Multiple Sclerosis. The Journal Of Immunology 2009, 183: 4067-4076. PMID: 19687098, PMCID: PMC2795331, DOI: 10.4049/jimmunol.0801888.Peer-Reviewed Original ResearchConceptsMyelin oligodendrocyte glycoproteinMultiple sclerosisB cell autoimmunityCell autoimmunityMOG-AbNative myelin oligodendrocyte glycoproteinPediatric-onset multiple sclerosisEarly onsetSurface AgPediatric MS casesPediatric-onset MSPediatric multiple sclerosisAdult-onset patientsCNS white matterHuman CNS white matterYears of ageAdult-onset diseaseDifferent myelin proteinsImmunological mechanismsPediatric patientsSerum AbsSuch autoantibodiesOligodendrocyte glycoproteinDisease onsetGlial cells
2007
Self-antigen tetramers discriminate between myelin autoantibodies to native or denatured protein
O'Connor KC, McLaughlin KA, De Jager PL, Chitnis T, Bettelli E, Xu C, Robinson WH, Cherry SV, Bar-Or A, Banwell B, Fukaura H, Fukazawa T, Tenembaum S, Wong SJ, Tavakoli NP, Idrissova Z, Viglietta V, Rostasy K, Pohl D, Dale RC, Freedman M, Steinman L, Buckle GJ, Kuchroo VK, Hafler DA, Wucherpfennig KW. Self-antigen tetramers discriminate between myelin autoantibodies to native or denatured protein. Nature Medicine 2007, 13: 211-217. PMID: 17237795, PMCID: PMC3429369, DOI: 10.1038/nm1488.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutoantibodiesEncephalomyelitis, Acute DisseminatedHumansImmunoassayMiceMultiple SclerosisMyelin ProteinsMyelin-Associated GlycoproteinMyelin-Oligodendrocyte GlycoproteinProtein FoldingSensitivity and SpecificityConceptsAcute disseminated encephalomyelitisMyelin oligodendrocyte glycoproteinMultiple sclerosisFluorescent-activated cell sortingRole of autoantibodiesExperimental autoimmune encephalomyelitisConformation-independent antibodiesDiscrimination of antibodiesMOG-specific autoantibodiesDisseminated encephalomyelitisMOG peptidesAutoimmune encephalomyelitisOligodendrocyte glycoproteinAutoantibody detectionTarget antigenAutoantibodiesMS casesELISA methodWestern blottingRadioimmunoassayAntibodiesEncephalomyelitisAntigen domainSensitive assayConformation-sensitive antibodies
2005
Antibodies from Inflamed Central Nervous System Tissue Recognize Myelin Oligodendrocyte Glycoprotein
O’Connor K, Appel H, Bregoli L, Call ME, Catz I, Chan JA, Moore NH, Warren KG, Wong SJ, Hafler DA, Wucherpfennig KW. Antibodies from Inflamed Central Nervous System Tissue Recognize Myelin Oligodendrocyte Glycoprotein. The Journal Of Immunology 2005, 175: 1974-1982. PMID: 16034142, PMCID: PMC4515951, DOI: 10.4049/jimmunol.175.3.1974.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAutoantibodiesBinding Sites, AntibodyCentral Nervous SystemDemyelinating Autoimmune Diseases, CNSFemaleFluoroimmunoassayHumansMaleMolecular Sequence DataMultiple SclerosisMyelin ProteinsMyelin-Associated GlycoproteinMyelin-Oligodendrocyte GlycoproteinRadioimmunoassaySolutionsConceptsMyelin oligodendrocyte glycoproteinMultiple sclerosisCNS diseaseOligodendrocyte glycoproteinCNS tissueChronic inflammatory CNS diseasesAutoantibody-mediated pathologyInflammatory CNS diseasesCentral nervous system tissueInflammatory CNS diseaseCases of encephalitisHigh-affinity autoantibodiesCases of subacuteNervous system tissueCNS parenchymaMOG autoantibodiesMS patientsOligodendrocyte lossMOG-AbCNS diseasesAutoantibodiesCerebrospinal fluidMOG proteinPostmortem casesControl tissues
2001
In vitro evidence that immunuaffinity-purified MOG contains immunogenic quantities of contaminating mouse IgG; techniques for producing Ig-free MOG
Ohashi T, Yukitake M, Slavin A, Krieger J, Hafler D. In vitro evidence that immunuaffinity-purified MOG contains immunogenic quantities of contaminating mouse IgG; techniques for producing Ig-free MOG. Journal Of Neuroimmunology 2001, 118: 194-202. PMID: 11498254, DOI: 10.1016/s0165-5728(01)00321-6.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalAntibody SpecificityBlotting, WesternCell LineClone CellsCytokinesElectrophoresis, Polyacrylamide GelEnzyme-Linked Immunosorbent AssayFlow CytometryHumansImmunoglobulin GImmunophenotypingImmunosorbent TechniquesLymphocyte ActivationMiceMultiple SclerosisMyelin ProteinsMyelin SheathMyelin-Associated GlycoproteinMyelin-Oligodendrocyte GlycoproteinSensitivity and SpecificityT-Lymphocytes