2004
Disease‐related epitope spread in a humanized T cell receptor transgenic model of multiple sclerosis
Ellmerich S, Takacs K, Mycko M, Waldner H, Wahid F, Boyton RJ, Smith PA, Amor S, Baker D, Hafler DA, Kuchroo VK, Altmann DM. Disease‐related epitope spread in a humanized T cell receptor transgenic model of multiple sclerosis. European Journal Of Immunology 2004, 34: 1839-1848. PMID: 15214032, DOI: 10.1002/eji.200324044.Peer-Reviewed Original ResearchConceptsHLA-DR15Multiple sclerosisTransgenic modelT cell receptor transgenic modelHLA class II moleculesHuman T cell clonesInduction of paralysisPoverty of movementHLA class IIT cell clonesClass II moleculesHuman TCR specificMBP 85Specific immunotherapyTCR specificMyelin epitopesT cellsIFN-gammaRodent modelsDiseaseCell clonesEpitopesDisease phenotypeSclerosisImmunization
1999
The distinction blurs between an autoimmune versus microbial hypothesis in multiple sclerosis
Hafler DA. The distinction blurs between an autoimmune versus microbial hypothesis in multiple sclerosis. Journal Of Clinical Investigation 1999, 104: 527-529. PMID: 10487765, PMCID: PMC483283, DOI: 10.1172/jci8193.Peer-Reviewed Original ResearchAnimalsAntigen PresentationAntigens, ViralAutoantigensAutoimmune DiseasesCardiovirus InfectionsCross ReactionsDemyelinating DiseasesDisease Models, AnimalDisease ProgressionEncephalomyelitis, Autoimmune, ExperimentalEpitopesHuman T-lymphotropic virus 1HumansMiceMicrogliaModels, ImmunologicalMolecular MimicryMultiple SclerosisMyelin ProteinsParaparesis, Tropical SpasticT-Lymphocyte SubsetsTheilovirusVirus Diseases
1998
Myelin basic protein reactive Th2 T cells are found in acute disseminated encephalomyelitis
Pohl-Koppe A, Burchett S, Thiele E, Hafler D. Myelin basic protein reactive Th2 T cells are found in acute disseminated encephalomyelitis. Journal Of Neuroimmunology 1998, 91: 19-27. PMID: 9846815, DOI: 10.1016/s0165-5728(98)00125-8.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, ViralAutoimmunityChildChild, PreschoolDemyelinating DiseasesEncephalomyelitis, Acute DisseminatedEncephalomyelitis, Autoimmune, ExperimentalEpitopesFemaleHerpes ZosterHerpesvirus 3, HumanHumansInfantInterferon-gammaInterleukin-2Interleukin-4MaleMyelin Basic ProteinT-LymphocytesConceptsAcute disseminated encephalomyelitisMBP-reactive T cell linesCentral nervous systemT cellsIL-4T cell linesDisseminated encephalomyelitisSignificant IFN-gamma secretionMyelin-reactive T cellsIFN-gamma secretionIL-4 secretionTh2 T cellsCell linesAutoimmune diseasesPredominant cytokineNormal subjectsSpontaneous recoveryNervous systemPatientsEncephalomyelitisCytokinesSecretionRecovery phaseCellsSubjects
1996
Downregulation of IL‐10 secretion and enhanced antigen‐presenting abilities following HTLV‐I infection of T cells
Scholz C, Hafler DA, Höllsberg P. Downregulation of IL‐10 secretion and enhanced antigen‐presenting abilities following HTLV‐I infection of T cells. Journal Of Neuroscience Research 1996, 45: 786-794. PMID: 8892090, DOI: 10.1002/(sici)1097-4547(19960915)45:6<786::aid-jnr15>3.0.co;2-u.Peer-Reviewed Original ResearchConceptsT cell clonesAntigen-presenting abilityHTLV-I infectionT cellsUninfected T cellsIL-10Immunosuppressive cytokine IL-10Human T-cell lymphotropic virus type ICD8 T cell proliferationMajor histocompatibility complex class IIPeripheral blood T cellsSpecific T cell clonesHistocompatibility complex class IILymphotropic virus type IGeneral immune activationHTLV-I myelopathySoluble peptide antigenCytokine IL-10IL-10 secretionEpstein-Barr virusAntigen-presenting cellsBlood T cellsInterferon-gamma secretionBest antigen-presenting cellsCytotoxic T cells
1995
T cell recognition of immunodominant and cryptic proteolipid protein epitopes in humans.
Markovic-Plese S, Fukaura H, Zhang J, al-Sabbagh A, Southwood S, Sette A, Kuchroo VK, Hafler DA. T cell recognition of immunodominant and cryptic proteolipid protein epitopes in humans. The Journal Of Immunology 1995, 155: 982-92. PMID: 7541828, DOI: 10.4049/jimmunol.155.2.982.Peer-Reviewed Original ResearchConceptsMultiple sclerosisT cellsPLP epitopesMHC class II isotypesPLP-reactive T cellsShort-term T cell linesCryptic epitopesProteolipid proteinT cell responsesT cell recognitionClass II isotypesT cell linesIndividual synthetic peptidesControl subjectsMHC restrictionImmune responseDR2 moleculesProliferative responseImmunodominant epitopesPLP peptidesProtein AgCell responsesCentral nervous system myelin proteinsMyelin proteinsEpitopesAntigen-specific therapies for the treatment of autoimmune diseases
Hafler D, Weiner H. Antigen-specific therapies for the treatment of autoimmune diseases. Seminars In Immunopathology 1995, 17: 61-76. PMID: 7482227, DOI: 10.1007/bf00194100.Peer-Reviewed Original ResearchA Review of T‐Cell Receptors in Multiple Sclerosis: Clonal Expansion and Persistence of Human T‐Cells Specific for an Immunodominant Myelin Basic Protein Peptidea
WUCHERPFENNIG K, HAFLER D. A Review of T‐Cell Receptors in Multiple Sclerosis: Clonal Expansion and Persistence of Human T‐Cells Specific for an Immunodominant Myelin Basic Protein Peptidea. Annals Of The New York Academy Of Sciences 1995, 756: 241-258. PMID: 7544075, DOI: 10.1111/j.1749-6632.1995.tb44522.x.Peer-Reviewed Original ResearchConceptsImmunodominant MBP peptidesT cell clonesMBP peptidesImmune responseNormal subjectsMBP-specific T cell clonesIndividual multiple sclerosis patientsTCR beta-chain usageMBP-specific T cellsTCR V beta chainsDR2 haplotypeSpecific T cell clonesBeta-chain usageT cell responsesAntigen-specific therapyMultiple sclerosis patientsSpecific T cellsDifferent T-cell linesT Cells SpecificIdentical TCR sequencesT cell receptorT cell linesAlpha-chain rearrangementMyelin antigensMS patients
1994
Regulatory T Cell Clones Induced by Oral Tolerance: Suppression of Autoimmune Encephalomyelitis
Chen Y, Kuchroo V, Inobe J, Hafler D, Weiner H. Regulatory T Cell Clones Induced by Oral Tolerance: Suppression of Autoimmune Encephalomyelitis. Science 1994, 265: 1237-1240. PMID: 7520605, DOI: 10.1126/science.7520605.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAmino Acid SequenceAnimalsCD4-Positive T-LymphocytesClone CellsEncephalomyelitis, Autoimmune, ExperimentalEpitopesImmune ToleranceInterleukin-10Interleukin-4Lymph NodesMajor Histocompatibility ComplexMesenteryMiceMolecular Sequence DataMyelin Basic ProteinMyelin ProteinsMyelin Proteolipid ProteinReceptors, Antigen, T-CellTransforming Growth Factor betaConceptsExperimental autoimmune encephalomyelitisMyelin basic proteinT cell clonesAutoimmune encephalomyelitisT cell receptor usageCell-mediated autoimmune diseaseMajor histocompatibility complex restrictionRegulatory T-cell clonesCell clonesMesenteric lymph nodesTh2-like clonesOral antigenOral toleranceEncephalitogenic CD4Lymph nodesPeripheral toleranceInterleukin-10Multiple sclerosisSJL miceAutoimmune diseasesOral administrationT cellsImmune responseInterleukin-4Animal models
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 studyCellsCD8Sclerosis
1991
The Potential of Restricted T Cell Recognition of Myelin Basic Protein Epitopes in the Therapy of Multiple Sclerosis
HAFLER D, MATSUI M, WUCHERPFENNIG K, OTA K, WEINER H. The Potential of Restricted T Cell Recognition of Myelin Basic Protein Epitopes in the Therapy of Multiple Sclerosis. Annals Of The New York Academy Of Sciences 1991, 636: 251-265. PMID: 1724362, DOI: 10.1111/j.1749-6632.1991.tb33456.x.Peer-Reviewed Original ResearchPresentation of autoantigen by human T cells.
LaSalle JM, Ota K, Hafler DA. Presentation of autoantigen by human T cells. The Journal Of Immunology 1991, 147: 774-80. PMID: 1713605, DOI: 10.4049/jimmunol.147.3.774.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAntigens, CDAntigens, Differentiation, T-LymphocyteAntigens, SurfaceAutoantigensCD2 AntigensCD58 AntigensEpitopesHistocompatibility AntigensHLA-D AntigensHumansIntegrin beta1Leukocyte Common AntigensLymphocyte ActivationLymphocyte Function-Associated Antigen-1Membrane GlycoproteinsMolecular Sequence DataMyelin Basic ProteinReceptors, ImmunologicT-LymphocytesConceptsT cell clonesMBP-reactive T cell clonesAutologous T cellsMyelin basic proteinMHC class IIT cellsHuman T cellsCell clonesAdhesion molecules LFA-3Class IIReactive T cell clonesWhole myelin basic proteinPresentation of autoantigensT cell interactionsActivated T cellsT cell presentationTCR-mediated responsesAg preparationsImmune responseMHC classSelf-AgForeign AgsInflammatory sitesCell presentationLFA-3
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
1989
Sequestration of virus-specific T cells in the cerebrospinal fluid of a patient with varicella zoster viral meningoencephalitis
Duby A, Weiner H, Benjamin D, Seidman JG, Hafler D. Sequestration of virus-specific T cells in the cerebrospinal fluid of a patient with varicella zoster viral meningoencephalitis. Journal Of Neuroimmunology 1989, 22: 63-68. PMID: 2465314, DOI: 10.1016/0165-5728(89)90010-6.Peer-Reviewed Original ResearchConceptsT cell clonesVirus-specific T cellsT cellsCerebrospinal fluidViral meningoencephalitisImmune responseViral infectionHerpes zoster viral infectionAntigen-specific T cellsT-cell receptor beta-chain gene rearrangementBeta-chain gene rearrangementsT cell responsesPatient's cerebrospinal fluidSecondary immune responseT-cell antigen receptor beta-chain geneBeta-chain geneMyelin basic proteinVZV meningoencephalitisMumps virusMeningoencephalitisPatientsClonal expansionGene rearrangementsBlot analysisInfectionMS: a CNS and systematic autoimmune disease
Hafler D, Weiner H. MS: a CNS and systematic autoimmune disease. Trends In Immunology 1989, 10: 104-107. PMID: 2472810, DOI: 10.1016/0167-5699(89)90236-3.Peer-Reviewed Original ResearchConceptsPeripheral immune compartmentCentral nervous systemImmune compartmentMultiple sclerosisImmunoregulatory defectsMS patientsAutoimmune diseasesCNS inflammatory responsesTotal lymphoid irradiationProgressive multiple sclerosisT-cell abnormalitiesB cell hyperactivitySystemic lupus erythematosusT cell functionSystematic autoimmune diseaseActivated T cellsLymphoid irradiationDisease activityImmune abnormalitiesSystemic treatmentLupus erythematosusRheumatoid arthritisPeripheral bloodInflammatory diseasesInflammatory response
1988
Anti-CD4 and anti-CD2 monoclonal antibody infusions in subjects with multiple sclerosis. Immunosuppressive effects and human anti-mouse responses.
Hafler DA, Ritz J, Schlossman SF, Weiner HL. Anti-CD4 and anti-CD2 monoclonal antibody infusions in subjects with multiple sclerosis. Immunosuppressive effects and human anti-mouse responses. The Journal Of Immunology 1988, 141: 131-8. PMID: 2454256, DOI: 10.4049/jimmunol.141.1.131.Peer-Reviewed Original ResearchConceptsHuman anti-mouse antibodiesAnti-mouse responseAnti-mouse antibodiesHuman anti-mouse responseMultiple sclerosisChronic progressive multiple sclerosisPhase I clinical studyAnti-CD2 monoclonal antibodiesProgressive multiple sclerosisMore chronic diseasesT cell subpopulationsHuman immune responseT cell activationAcute immunosuppressionMAb infusionsT cell surfaceAnti-CD4Daily infusionsImmunologic responseImmunosuppressive effectsChronic diseasesIgG isotypeClinical studiesImmune responseLike antibodies