2013
Serum autoantibodies to myelin peptides distinguish acute disseminated encephalomyelitis from relapsing– remitting multiple sclerosis
Van Haren K, Tomooka BH, Kidd BA, Banwell B, Bar-Or A, Chitnis T, Tenembaum SN, Pohl D, Rostasy K, Dale RC, O’Connor K, Hafler DA, Steinman L, Robinson WH. Serum autoantibodies to myelin peptides distinguish acute disseminated encephalomyelitis from relapsing– remitting multiple sclerosis. Multiple Sclerosis Journal 2013, 19: 1726-1733. PMID: 23612879, PMCID: PMC4411183, DOI: 10.1177/1352458513485653.Peer-Reviewed Original ResearchConceptsAcute disseminated encephalomyelitisMyelin basic proteinDisseminated encephalomyelitisMyelin peptidesMultiple sclerosisIgM autoantibodiesIsotype-specific secondary antibodiesPediatric acute disseminated encephalomyelitisRelapsing-remitting multiple sclerosisPediatric multiple sclerosisProteolipid proteinMicroarrays softwareBasic proteinMyelin antigensLaboratory featuresPeptide autoantibodiesMS seraSerum autoantibodiesIgG autoantibodiesAutoantibody biomarkersSerum IgGOligodendrocyte-specific proteinAutoantibody reactivityAdult MSAutoantibodies
2009
Antibodies produced by clonally expanded plasma cells in multiple sclerosis cerebrospinal fluid
Owens GP, Bennett JL, Lassmann H, O'Connor KC, Ritchie AM, Shearer A, Lam C, Yu X, Birlea M, DuPree C, Williamson RA, Hafler DA, Burgoon MP, Gilden D. Antibodies produced by clonally expanded plasma cells in multiple sclerosis cerebrospinal fluid. Annals Of Neurology 2009, 65: 639-649. PMID: 19557869, PMCID: PMC2843543, DOI: 10.1002/ana.21641.Peer-Reviewed Original ResearchConceptsMS cerebrospinal fluidMyelin oligodendrocyte glycoproteinMultiple sclerosisCerebrospinal fluidMyelin basic proteinMyelin antigensOligodendrocyte glycoproteinMultiple sclerosis cerebrospinal fluidOligoclonal B cell responseB cell clonal expansionIntrathecal IgG synthesisB cell responsesPlasma cell cloneB lymphocyte clonesHuman brain tissue sectionsTissue sectionsProteolipid proteinIndividual myelin proteinsBasic proteinBrain tissue sectionsIgG synthesisInflammatory cellsHumoral responseControl brainsPlasma cells
2004
PD-1 ligands, negative regulators for activation of naïve, memory, and recently activated human CD4+ T cells
Cai G, Karni A, Oliveira EM, Weiner HL, Hafler DA, Freeman GJ. PD-1 ligands, negative regulators for activation of naïve, memory, and recently activated human CD4+ T cells. Cellular Immunology 2004, 230: 89-98. PMID: 15598424, DOI: 10.1016/j.cellimm.2004.09.004.Peer-Reviewed Original ResearchConceptsPD-1 ligand blockadeT cellsPD-L1Myelin basic proteinPD-L2Human CD4Ex vivo dendritic cellsVivo dendritic cellsPD-1 ligandsPD-1 pathwayPrimary responseActivation of naïveNaive T cellsPD-1Dendritic cellsCytokine productionNormal donorsIFN-gammaSecondary responseCD4BlockadeHigh expressionNegative regulatory pathwaysInduced activationBasic protein
2003
Myelin basic protein-reactive autoantibodies in the serum and cerebrospinal fluid of multiple sclerosis patients are characterized by low-affinity interactions
O'Connor KC, Chitnis T, Griffin DE, Piyasirisilp S, Bar-Or A, Khoury S, Wucherpfennig KW, Hafler DA. Myelin basic protein-reactive autoantibodies in the serum and cerebrospinal fluid of multiple sclerosis patients are characterized by low-affinity interactions. Journal Of Neuroimmunology 2003, 136: 140-148. PMID: 12620653, DOI: 10.1016/s0165-5728(03)00002-x.Peer-Reviewed Original ResearchConceptsMyelin basic proteinMultiple sclerosisCerebrospinal fluidSoluble myelin basic proteinSemple rabies vaccinePresence of autoantibodiesMultiple sclerosis patientsSera of patientsFraction of patientsAnti-MBP antibodiesHigh-affinity autoantibodiesBasic proteinMBP autoantibodiesRelevant autoantibodiesMS patientsSclerosis patientsAutoimmune diseasesHumoral responseRabies vaccineAutoantibodiesPatientsImmunodominant antigensSerumDiseaseSolid-phase assays
1997
Direct Ex Vivo Analysis of Activated, Fas-sensitive Autoreactive T Cells in Human Autoimmune Disease
Bieganowska K, Ausubel L, Modabber Y, Slovik E, Messersmith W, Hafler D. Direct Ex Vivo Analysis of Activated, Fas-sensitive Autoreactive T Cells in Human Autoimmune Disease. Journal Of Experimental Medicine 1997, 185: 1585-1594. PMID: 9151896, PMCID: PMC2196290, DOI: 10.1084/jem.185.9.1585.Peer-Reviewed Original ResearchConceptsAutoreactive T cellsT cellsMultiple sclerosisPersistent T cellsT cell frequenciesHuman autoimmune diseasesSubpopulation of patientsT cell clonesT cell receptorSingle T cellsMyelin basic proteinAutoimmune diseasesAutoantigenic peptidesAntigen stimulationDirect exCell frequencyTCR transcriptsFlow cytometryCell receptorCell clonesBeta chainHigh frequencyCell deathBasic proteinChain transcripts
1995
Reactivity of normal T-cell lines to MBP isolated from normal and multiple sclerosis white matter
McLaurin J, Hafler D, Antel J. Reactivity of normal T-cell lines to MBP isolated from normal and multiple sclerosis white matter. Journal Of The Neurological Sciences 1995, 128: 205-211. PMID: 7537795, DOI: 10.1016/0022-510x(94)00224-c.Peer-Reviewed Original ResearchConceptsT cell linesMyelin basic proteinMS white matterCentral nervous systemWhite matterMBP preparationsMS brainsPeripheral bloodRegion of MBPMultiple sclerosis white matterMBP-reactive T cell linesReactive T cell linesHuman T cell clonesT cell reactivityMultiple sclerosis patientsAutologous peripheral bloodNormal T-cell linesConcentration-response curvesT cell clonesAdult white matterHuman myelin basic proteinBasic proteinMS patientsSclerosis patientsMononuclear cells
1994
Increased frequency of interleukin 2-responsive T cells specific for myelin basic protein and proteolipid protein in peripheral blood and cerebrospinal fluid of patients with multiple sclerosis.
Zhang J, Markovic-Plese S, Lacet B, Raus J, Weiner HL, Hafler DA. Increased frequency of interleukin 2-responsive T cells specific for myelin basic protein and proteolipid protein in peripheral blood and cerebrospinal fluid of patients with multiple sclerosis. Journal Of Experimental Medicine 1994, 179: 973-984. PMID: 7509366, PMCID: PMC2191414, DOI: 10.1084/jem.179.3.973.Peer-Reviewed Original ResearchConceptsMyelin-reactive T cellsFrequency of MBPMBP-reactive T cell linesMBP-reactive T cellsMyelin basic proteinT cellsCerebrospinal fluidT cell linesMS patientsProteolipid proteinPLP-reactive T cellsNormal individualsFrequency of interleukinAutoreactive T cellsPathogenesis of MSMultiple sclerosis patientsIL-2-responsive cellsRIL-2 stimulationCentral nervous systemCell linesBasic proteinSclerosis patientsMultiple sclerosisPeripheral bloodPathogenic role
1993
MHC-Restricted Depletion of Human Myelin Basic Protein-Reactive T Cells by T Cell Vaccination
Zhang J, Medaer R, Stinissen P, Hafler D, Raus J. MHC-Restricted Depletion of Human Myelin Basic Protein-Reactive T Cells by T Cell Vaccination. Science 1993, 261: 1451-1454. PMID: 7690157, DOI: 10.1126/science.7690157.Peer-Reviewed Original ResearchConceptsAutoreactive T cellsT cell vaccinationT cellsT cell linesCell vaccinationMyelin basic protein-reactive T cellsRegulatory T cell linesMBP-reactive T cellsExperimental autoimmune diseasesReactive T cellsT cell responsesMajor histocompatibility antigensCell linesMyelin basic proteinMultiple sclerosisAutoimmune diseasesHistocompatibility antigensCell responsesVaccinationBasic proteinRecipientsPresent studyCellsCD8SclerosisBiological activity of recombinant human myelin basic protein
Oettinger H, Al-Sabbagh A, Jingwu Z, LaSalle J, Weiner H, Hafler D. Biological activity of recombinant human myelin basic protein. Journal Of Neuroimmunology 1993, 44: 157-162. PMID: 7685037, DOI: 10.1016/0165-5728(93)90037-y.Peer-Reviewed Original ResearchConceptsRecombinant human myelin basic proteinRecombinant protein bindsRecombinant MBPInducible expression vectorBasic proteinMyelin basic proteinRecombinant protein preparationsProtein bindsHuman myelin basic proteinRecombinant proteinsExpression vectorEscherichia coliProtein preparationsProteinNative MBPE. coliCation exchange chromatographySDS-PAGEBiological reagentsSimilar affinityHuman MBPColiBiological activitySimilar conformationsCell clonesDouble-Blind Pilot Trial of Oral Tolerization with Myelin Antigens in Multiple Sclerosis
Weiner H, Mackin G, Matsui M, Orav E, Khoury S, Dawson D, Hafler D. Double-Blind Pilot Trial of Oral Tolerization with Myelin Antigens in Multiple Sclerosis. Science 1993, 259: 1321-1324. PMID: 7680493, DOI: 10.1126/science.7680493.Peer-Reviewed Original ResearchConceptsMultiple sclerosisOral tolerizationMyelin antigensAutoimmune diseasesDouble-blind pilot trialRelapsing-remitting multiple sclerosisDouble-blind studyCentral nervous systemMyelin basic proteinMajor exacerbationsDaily capsuleT cellsT lymphocytesPilot trialSide effectsNervous systemControl groupMyelin componentsBovine myelinDiseaseMyelinTolerizationSclerosisAntigenBasic protein
1992
Experimental Approaches to Specific Immunotherapy in Multiple Sclerosis
Hafler D, Brod S, Weiner H. Experimental Approaches to Specific Immunotherapy in Multiple Sclerosis. Clinical Medicine And The Nervous System 1992, 301-307. DOI: 10.1007/978-1-4471-3184-7_15.Peer-Reviewed Original ResearchMultiple sclerosisT cellsAutoimmune diseasesNervous systemAutoreactive T cellsPatient T cellsCentral nervous systemInitial inductionMyelin basic proteinSpecific immunotherapyImmune targetsWhite matter structuresImmune regulationProteolipid proteinSclerosisMatter structuresDiseaseBasic proteinDestructive processesImmunotherapyDemyelinationInflammationCareful regulation
1991
T-cell recognition of myelin basic protein
Wucherpfennig K, Weiner H, Hafler D. T-cell recognition of myelin basic protein. Trends In Immunology 1991, 12: 277-282. PMID: 1716903, DOI: 10.1016/0167-5699(91)90126-e.Peer-Reviewed Original ResearchSuppression of experimental autoimmune encephalomyelitis by oral administration of myelin antigens: IV. Suppression of chronic relapsing disease in the lewis rat and strain 13 guinea pig
Brod S, al‐Sabbagh A, Sobel R, Hafler D, Weiner H. Suppression of experimental autoimmune encephalomyelitis by oral administration of myelin antigens: IV. Suppression of chronic relapsing disease in the lewis rat and strain 13 guinea pig. Annals Of Neurology 1991, 29: 615-622. PMID: 1716432, DOI: 10.1002/ana.410290608.Peer-Reviewed Original ResearchConceptsExperimental autoimmune encephalomyelitisAutoimmune encephalomyelitisMyelin antigensGuinea pig myelinOral administrationCentral nervous systemLewis ratsMyelin basic proteinAntigen-specific peripheral immune toleranceGuinea pigsMonophasic experimental autoimmune encephalomyelitisDelayed-type hypersensitivity responseGuinea pig myelin basic proteinHuman demyelinating disordersOngoing immune responsePig myelin basic proteinComplete Freund's adjuvantPeripheral immune toleranceExacerbation of diseaseHuman autoimmune diseasesBasic proteinClinical relapseDemyelinating disorderOral toleranceCNS demyelination
1990
T-cell recognition of an immuno-dominant myelin basic protein epitope in multiple sclerosis
Ota K, Matsui M, Milford E, Mackin G, Weiner H, Hafler D. T-cell recognition of an immuno-dominant myelin basic protein epitope in multiple sclerosis. Nature 1990, 346: 183-187. PMID: 1694970, DOI: 10.1038/346183a0.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAntigen-Presenting CellsApoproteinsAutoantigensCells, CulturedEpitopesHLA-DR AntigensHumansIn Vitro TechniquesMajor Histocompatibility ComplexMolecular Sequence DataMultiple SclerosisMyelin Basic ProteinMyelin ProteinsMyelin Proteolipid ProteinPeptide FragmentsT-LymphocytesConceptsMultiple sclerosis patientsT cell linesMyelin basic proteinMultiple sclerosisSclerosis patientsT cellsVivo-activated T cellsShort-term T cell linesMyelin basic protein epitopeBasic proteinExperimental autoimmune encephalomyelitisDifferent T-cell linesCentral nervous systemMultiple sclerosis subjectsT cell recognitionT cell specificityAutoimmune encephalomyelitisImmune involvementAutoimmune diseasesPotential autoantigensNormal controlsNervous systemNeurological diseasesSclerosisPatientsShared Human T Cell Receptor Vβ Usage to Immunodominant Regions of Myelin Basic Protein
Wucherpfennig K, Ota K, Endo N, Seidman JG, Rosenzweig A, Weiner H, Hafler D. Shared Human T Cell Receptor Vβ Usage to Immunodominant Regions of Myelin Basic Protein. Science 1990, 248: 1016-1019. PMID: 1693015, DOI: 10.1126/science.1693015.Peer-Reviewed Original ResearchConceptsMultiple sclerosisImmunodominant regionMyelin basic proteinMS patientsT cellsBeta 17T cell receptor Vβ usageTCR V beta gene usageReactive T cellsBeta gene usageT cell receptor beta chainT cell linesBasic proteinSpecific immunotherapyVβ usageAutoimmune diseasesReceptor beta chainHealthy subjectsTarget antigenGene usageBeta 12Myelin proteinsTCR structureHuman MBPBeta chain
1987
Myelin basic protein and proteolipid protein reactivity of brain- and cerebrospinal fluid-derived T cell clones in multiple sclerosis and postinfectious encephalomyelitis.
Hafler DA, Benjamin DS, Burks J, Weiner HL. Myelin basic protein and proteolipid protein reactivity of brain- and cerebrospinal fluid-derived T cell clones in multiple sclerosis and postinfectious encephalomyelitis. The Journal Of Immunology 1987, 139: 68-72. PMID: 2438352, DOI: 10.4049/jimmunol.139.1.68.Peer-Reviewed Original ResearchConceptsT cell clonesMyelin basic proteinPeripheral bloodPostinfectious encephalomyelitisCell clonesMultiple sclerosisT cellsProteolipid proteinPeripheral blood T cell clonesBlood T-cell clonePlaque tissueMS plaque tissueProportion of T4T cell reactivityHuman myelin basic proteinBasic proteinMS patientsCell reactivityIL-2Cerebrospinal fluidTarget antigenClear reactivityBrain tissueBloodEncephalomyelitis
1986
Cell-mediated immunity to myelin-associated glycoprotein, proteolipid protein, and myelin basic protein in multiple sclerosis
Johnson D, Hafler D, Fallis R, Lees M, Brady R, Quarles R, Weiner H. Cell-mediated immunity to myelin-associated glycoprotein, proteolipid protein, and myelin basic protein in multiple sclerosis. Journal Of Neuroimmunology 1986, 13: 99-108. PMID: 2428837, DOI: 10.1016/0165-5728(86)90053-6.Peer-Reviewed Original ResearchConceptsActive MS patientsMyelin basic proteinPeripheral blood lymphocytesMyelin antigensMS patientsControl subjectsActive MSMultiple sclerosisNeurologic diseaseProteolipid proteinStable multiple sclerosis patientsMean proliferative responseCell-mediated immunityMultiple sclerosis patientsBasic proteinStable MSOND groupSclerosis patientsT8 subsetsBlood lymphocytesLymphocyte stimulationProliferative responseProportion of individualsPatientsAntigen
1985
Phenotypic and functional analysis of T cells cloned directly from the blood and cerebrospinal fluid of patients with multiple sclerosis
Hafler D, Buchsbaum M, Johnson D, Weiner H. Phenotypic and functional analysis of T cells cloned directly from the blood and cerebrospinal fluid of patients with multiple sclerosis. Annals Of Neurology 1985, 18: 451-458. PMID: 2416267, DOI: 10.1002/ana.410180407.Peer-Reviewed Original ResearchConceptsMultiple sclerosisBlood of patientsT cellsMyelin basic proteinCerebrospinal fluid lymphocytesT-cell abnormalitiesCSF of patientsAntigen-specific cellsIndividual T cellsBasic proteinSuppressor cellsViral meningoencephalitisStimulating lymphocytesInterleukin-2Antigen reactivityCell abnormalitiesCerebrospinal fluidSingle cell clonal analysisPatientsT8 populationWhite matterBloodCSFSclerosisLymphocytes
1980
Antibodies to Myelin Basic Protein in Cerebrospinal Fluid of Patients with Multiple Sclerosis
Panitch H, Hafler D, Johnson K. Antibodies to Myelin Basic Protein in Cerebrospinal Fluid of Patients with Multiple Sclerosis. 1980, 98-105. DOI: 10.1007/978-3-642-67554-6_17.Peer-Reviewed Original ResearchMyelin basic proteinMultiple sclerosisCerebrospinal fluidSolid-phase radioimmunoassayBasic proteinActive diseaseAutoimmune responseOligoclonal bandsCSF IgGIgG classIgG concentrationsPatientsPhase radioimmunoassayAntibodiesSclerosisDiseaseNonspecific adherenceRemissionPathogenesisIgGAntigenRadioimmunoassay