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
2005
High Incidence of Spontaneous Disease in an HLA-DR15 and TCR Transgenic Multiple Sclerosis Model
Ellmerich S, Mycko M, Takacs K, Waldner H, Wahid FN, Boyton RJ, King RH, Smith PA, Amor S, Herlihy AH, Hewitt RE, Jutton M, Price DA, Hafler DA, Kuchroo VK, Altmann DM. High Incidence of Spontaneous Disease in an HLA-DR15 and TCR Transgenic Multiple Sclerosis Model. The Journal Of Immunology 2005, 174: 1938-1946. PMID: 15699121, DOI: 10.4049/jimmunol.174.4.1938.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigen PresentationCell MovementCentral Nervous SystemDisease Models, AnimalDisease ProgressionDNA-Binding ProteinsEpitopes, T-LymphocyteHLA-DR AntigensHLA-DR Serological SubtypesMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicMultiple SclerosisMyelin Basic ProteinParalysisPeptide FragmentsReceptors, Antigen, T-Cell, alpha-betaT-Lymphocyte SubsetsConceptsT cell responsesHLA-DR15Multiple sclerosisDeterminant spreadSpontaneous diseaseCell responsesCD4 T cell recognitionCNS tissue damageHuman multiple sclerosisMultiple sclerosis modelT cell reactivityExperimental allergic encephalomyelitisMyelin oligodendrocyte glycoproteinT cell recognitionMyelin basic proteinAllergic encephalomyelitisMyelin epitopesPeptide immunotherapyAxonal degenerationCell reactivityOligodendrocyte glycoproteinPathogenic roleT cellsHigh incidenceTransgenic mice
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 proteinCross-Reactive TCR Responses to Self Antigens Presented by Different MHC Class II Molecules
Mycko MP, Waldner H, Anderson DE, Bourcier KD, Wucherpfennig KW, Kuchroo VK, Hafler DA. Cross-Reactive TCR Responses to Self Antigens Presented by Different MHC Class II Molecules. The Journal Of Immunology 2004, 173: 1689-1698. PMID: 15265898, DOI: 10.4049/jimmunol.173.3.1689.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAmino Acid SubstitutionAnimalsAntigen PresentationAutoantigensCD4 AntigensCross ReactionsEncephalomyelitis, Autoimmune, ExperimentalHLA-DR alpha-ChainsHLA-DR AntigensHLA-DRB1 ChainsHumansHybridomasL CellsLymphocyte ActivationMembrane ProteinsMiceMolecular Sequence DataMultiple Sclerosis, Relapsing-RemittingMyelin Basic ProteinPeptide FragmentsPhosphorylationProtein Processing, Post-TranslationalReceptors, Antigen, T-CellReceptors, Antigen, T-Cell, alpha-betaT-Lymphocyte SubsetsTransfectionConceptsAutoreactive T cellsMHC class II moleculesClass II moleculesT cellsSpontaneous experimental autoimmune encephalomyelitisRelapsing-remitting multiple sclerosisDifferent MHC class II moleculesExperimental autoimmune encephalomyelitisAltered peptide ligandTh cell clonesT cell hybridomasMyelin basic proteinAutoimmune encephalomyelitisMultiple sclerosisSelf antigensCD4 coreceptorRestriction elementsHealthy individualsDiseased patientsHuman TCRPatientsTCR responsesCell clonesCell hybridomasPeptide ligands
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 assaysCTLA-4 dysregulation in the activation of myelin basic protein reactive T cells may distinguish patients with multiple sclerosis from healthy controls
Oliveira EM, Bar-Or A, Waliszewska AI, Cai G, Anderson DE, Krieger JI, Hafler DA. CTLA-4 dysregulation in the activation of myelin basic protein reactive T cells may distinguish patients with multiple sclerosis from healthy controls. Journal Of Autoimmunity 2003, 20: 71-81. PMID: 12604314, DOI: 10.1016/s0896-8411(02)00106-3.Peer-Reviewed Original ResearchConceptsMultiple sclerosisT cellsMyelin basic proteinHealthy controlsMyelin basic protein-reactive T cellsMBP-reactive T cellsPathogenesis of MSPeripheral blood mononuclear cellsCTLA-4 blockadeReactive T cellsBlood mononuclear cellsCo-stimulatory pathwaysNaïve T cellsCo-stimulatory signalsCentral nervous systemCTLA-4 engagementCytokine responsesAutoimmune responseMononuclear cellsInflammatory diseasesB7-CD28Proliferative responseNervous systemPatientsMyelin sheath
1999
Cross-Reactivity of Borrelia burgdorferi and Myelin Basic Protein-Specific T Cells Is Not Observed in Borrelial Encephalomyelitis
Pohl-Koppe A, Logigian E, Steere A, Hafler D. Cross-Reactivity of Borrelia burgdorferi and Myelin Basic Protein-Specific T Cells Is Not Observed in Borrelial Encephalomyelitis. Cellular Immunology 1999, 194: 118-123. PMID: 10357888, DOI: 10.1006/cimm.1999.1495.Peer-Reviewed Original ResearchConceptsMyelin basic proteinT cell linesB. burgdorferiMyelin basic protein-specific T cellsT cell autoimmune responsesShort-term T cell linesLate Lyme diseaseT cell responsesT cell clonesWhite matter diseaseMyelin antigensTransverse myelitisRare manifestationAutoimmune responseMultiple sclerosisPathogenetic roleHealthy controlsT cellsLike diseaseWhite matterPatientsEncephalomyelitisLyme borreliosisLyme diseaseBorrelia burgdorferiCross-Reactivity of T-Cell Clones Specific for Altered Peptide Ligands of Myelin Basic Protein
Ausubel L, Bieganowska K, Hafler D. Cross-Reactivity of T-Cell Clones Specific for Altered Peptide Ligands of Myelin Basic Protein. Cellular Immunology 1999, 193: 99-107. PMID: 10202117, DOI: 10.1006/cimm.1998.1447.Peer-Reviewed Original ResearchConceptsT cell clonesT cellsSpecific T cell repertoireAutoreactive T cellsTh1-type cytokinesTh2-type cytokinesMultiple sclerosis patientsT cell repertoireAltered peptide ligandT cell receptor alphaPotential beneficial effectsTCR contact residuesMyelin basic proteinDownregulatory cytokinesSclerosis patientsIL-4IL-5Individual patientsReceptor alphaBeneficial effectsClonal expansionCytokinesPeptide ligandsSubstantial proliferationCross reactivity
1998
Cytokine secretion of myelin basic protein reactive T cells in patients with multiple sclerosis
Windhagen A, Anderson DE, Carrizosa A, Balashov K, Weiner HL, Hafler DA. Cytokine secretion of myelin basic protein reactive T cells in patients with multiple sclerosis. Journal Of Neuroimmunology 1998, 91: 1-9. PMID: 9846813, DOI: 10.1016/s0165-5728(98)00086-1.Peer-Reviewed Original ResearchConceptsMBP-reactive T cellsReactive T cellsChronic progressive multiple sclerosisProgressive multiple sclerosisMultiple sclerosisT cellsCytokine secretionMyelin basic proteinT cell linesNormal controlsMyelin basic protein-reactive T cellsAntigen-specific cytokine secretionMyelin-reactive T cellsNormal individualsShort-term T cell linesAutoreactive T cell linesCP MS patientsIL-12/IL-4/MBP-reactive cellsTh2-type phenotypeRR-MS patientsTh2 cytokine secretionAutoreactive T cellsMore IFN-gammaPulse Cyclophosphamide Plus Methylprednisolone Induces Myelin-Antigen-Specific IL-4-Secreting T Cells in Multiple Sclerosis Patients
Takashima H, Smith D, Fukaura H, Khoury S, Hafler D, Weiner H. Pulse Cyclophosphamide Plus Methylprednisolone Induces Myelin-Antigen-Specific IL-4-Secreting T Cells in Multiple Sclerosis Patients. Clinical Immunology 1998, 88: 28-34. PMID: 9683547, DOI: 10.1006/clin.1998.4558.Peer-Reviewed Original ResearchConceptsIL-4-secreting T cellsUntreated MS patientsProgressive MS patientsT cell linesMS patientsIL-4 secretionMyelin basic proteinT cellsMultiple sclerosisMyelin antigensTetanus toxoidTh1-type autoimmune diseaseShort-term T cell linesCell linesPulse cyclophosphamide therapyTh2-type responseIL-4 productionMultiple sclerosis patientsIFN-gamma productionProteolipid proteinImmune deviationPulse cyclophosphamideCyclophosphamide therapySclerosis patientsAutoimmune diseasesExpansion of autoreactive T cells in multiple sclerosis is independent of exogenous B7 costimulation.
Scholz C, Patton K, Anderson D, Freeman G, Hafler D. Expansion of autoreactive T cells in multiple sclerosis is independent of exogenous B7 costimulation. The Journal Of Immunology 1998, 160: 1532-8. PMID: 9570577, DOI: 10.4049/jimmunol.160.3.1532.Peer-Reviewed Original ResearchMeSH KeywordsAbataceptAntigens, CDAntigens, DifferentiationAutoantigensB7-1 AntigenB7-2 AntigenClone CellsCTLA-4 AntigenEpitopes, T-LymphocyteHumansImmunoconjugatesImmunoglobulin Fc FragmentsImmunosuppressive AgentsInterleukin-4Lymphocyte ActivationMembrane GlycoproteinsMultiple SclerosisMyelin Basic ProteinRecombinant Fusion ProteinsTetanus ToxoidThymidineT-Lymphocyte SubsetsConceptsCD4 T cellsMultiple sclerosisT cellsB7-1Myelin basic proteinPathogenesis of MSMyelin-reactive T cellsPeripheral blood T cellsB7-2 engagementAutoreactive T cellsBlood T cellsAbsence of costimulationCentral nervous systemAntigen-specific signalT cell activationMS patientsB7 costimulationInflammatory diseasesTetanus toxoidB7-2Normal controlsNormal subjectsCostimulatory signalsNervous systemCell activation
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
1996
IL-12 induces human T cells secreting IL-10 with IFN-gamma.
Windhagen A, Anderson DE, Carrizosa A, Williams RE, Hafler DA. IL-12 induces human T cells secreting IL-10 with IFN-gamma. The Journal Of Immunology 1996, 157: 1127-31. PMID: 8757617, DOI: 10.4049/jimmunol.157.3.1127.Peer-Reviewed Original ResearchConceptsIL-10T cell responsesIL-12T cell clonesIFN-gammaT cellsT cell linesHuman T cellsMyelin basic protein-reactive T cell clonesCell responsesPredominant T cell responseShort-term T cell linesConcomitant secretionHuman T cell responsesCell clonesAg-specific stimulationIFN-gamma secretionIFN-gamma productionAnti-CD3 mAbCell linesMyelin basic proteinGamma AbIL-2IL-4Cytokine secretionInduction of circulating myelin basic protein and proteolipid protein-specific transforming growth factor-beta1-secreting Th3 T cells by oral administration of myelin in multiple sclerosis patients.
Fukaura H, Kent SC, Pietrusewicz MJ, Khoury SJ, Weiner HL, Hafler DA. Induction of circulating myelin basic protein and proteolipid protein-specific transforming growth factor-beta1-secreting Th3 T cells by oral administration of myelin in multiple sclerosis patients. Journal Of Clinical Investigation 1996, 98: 70-77. PMID: 8690806, PMCID: PMC507402, DOI: 10.1172/jci118779.Peer-Reviewed Original ResearchConceptsMyelin basic proteinT cellsOral administrationAutoimmune diseasesTetanus toxoidT cell linesMS patientsMultiple sclerosisProteolipid proteinFrequency of MBPNon-treated MS patientsPLP-reactive T cellsTh1-type autoimmune diseaseShort-term T cell linesCell-mediated autoimmune diseaseRelapsing-remitting MS patientsOriginal T cell cloneSpecific IFN-gammaSystemic immune toleranceExperimental autoimmune diseasesRegulatory T cellsReactive T cellsIFN-gamma secretionMultiple sclerosis patientsT cell clones
1995
Modulation of cytokine patterns of human autoreactive T cell clones by a single amino acid substitution of their peptide ligand
Windhagen A, Schooz C, Höllsberg P, Fukaura H, Sette A, Hafler D. Modulation of cytokine patterns of human autoreactive T cell clones by a single amino acid substitution of their peptide ligand. Immunity 1995, 2: 373-380. PMID: 7536622, DOI: 10.1016/1074-7613(95)90145-0.Peer-Reviewed Original ResearchConceptsT cell clonesCytokine patternCell clonesHuman autoreactive T cell clonesT cell cytokine secretionAutoreactive T cell clonesT cell receptor contact residuesIL-4 secretionAltered peptide ligandMajor histocompatability complexPresence of ionomycinMyelin basic proteinIL-10Receptor contact residuesIL-4IL-2TCR antagonistsCytokine secretionImmune responseIFN-gammaPeptide ligandsProtein secretionCalcium fluxMature T-cell clonesSecretionReactivity 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
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 modelsClonal expansion and persistence of human T cells specific for an immunodominant myelin basic protein peptide.
Wucherpfennig KW, Zhang J, Witek C, Matsui M, Modabber Y, Ota K, Hafler DA. Clonal expansion and persistence of human T cells specific for an immunodominant myelin basic protein peptide. The Journal Of Immunology 1994, 152: 5581-92. PMID: 7514641, DOI: 10.4049/jimmunol.152.11.5581.Peer-Reviewed Original ResearchConceptsT cellsNormal subjectsImmunodominant myelin basic protein peptideMBP-specific T cell linesDR2 haplotypeSpecific T cell clonesTCR beta-chain sequencesReactive T cellsT cell responsesHLA-DR moleculesT cell clonesIdentical TCR sequencesMyelin basic protein peptideIL-2 stimulationT cell linesHuman T cellsAlpha-chain rearrangementMyelin basic proteinMultiple sclerosisBeta chain sequencesTCR rearrangementsPatientsCell responsesTCR alphaTCR sequencesT cell receptor (TCR) usage determines disease susceptibility in experimental autoimmune encephalomyelitis: studies with TCR V beta 8.2 transgenic mice.
Kuchroo VK, Collins M, al-Sabbagh A, Sobel RA, Whitters MJ, Zamvil SS, Dorf ME, Hafler DA, Seidman JG, Weiner HL. T cell receptor (TCR) usage determines disease susceptibility in experimental autoimmune encephalomyelitis: studies with TCR V beta 8.2 transgenic mice. Journal Of Experimental Medicine 1994, 179: 1659-1664. PMID: 8163944, PMCID: PMC2191471, DOI: 10.1084/jem.179.5.1659.Peer-Reviewed Original ResearchConceptsExperimental allergic encephalomyelitisMyelin basic proteinAutoimmune diseasesEncephalitogenic epitopeTCR repertoireTCR VProteolipid proteinTransgenic miceT cell receptor usageDiverse T cell repertoireT cell receptor repertoireExperimental autoimmune encephalomyelitisAutoreactive T cellsCell receptor repertoireT cell repertoireT cell clonesAutoimmune encephalomyelitisAllergic encephalomyelitisSJL miceT cellsCell repertoirePLP epitopesReceptor usageReceptor repertoireImmunization