2012
Class II MHC Self-Antigen Presentation in Human B and T Lymphocytes
Costantino CM, Spooner E, Ploegh HL, Hafler DA. Class II MHC Self-Antigen Presentation in Human B and T Lymphocytes. PLOS ONE 2012, 7: e29805. PMID: 22299025, PMCID: PMC3267721, DOI: 10.1371/journal.pone.0029805.Peer-Reviewed Original ResearchMeSH KeywordsAntigen PresentationAntigen-Antibody ComplexAutoantigensB-LymphocytesBlood DonorsCase-Control StudiesCD4-Positive T-LymphocytesCell Line, TransformedHistocompatibility Antigens Class IIHLA-DR AntigensHumansModels, BiologicalPeptidesProteomeSpectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationT-LymphocytesTandem Mass SpectrometryConceptsHLA-DRT cellsPeptide repertoireSelf-antigen presentationAntigen presenting cellsEndogenous peptide repertoireB cell repertoireT-cell processMHC-peptide complexesIL-2Presenting cellsAPC typesT lymphocytesCell repertoireNovel epitopesB cellsHuman BEndogenous epitopesClass II MHC-peptide complexesPeptide epitopesEpitopesCellsCell processesCell-specific proteomesVast majority
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
2010
Population structure and HLA DRB1*1501 in the response of subjects with multiple sclerosis to first-line treatments
Gross R, Healy BC, Cepok S, Chitnis T, Khoury SJ, Hemmer B, Weiner HL, Hafler DA, De Jager PL. Population structure and HLA DRB1*1501 in the response of subjects with multiple sclerosis to first-line treatments. Journal Of Neuroimmunology 2010, 233: 168-174. PMID: 21115201, DOI: 10.1016/j.jneuroim.2010.10.038.Peer-Reviewed Original ResearchA Major Histocompatibility Class I Locus Contributes to Multiple Sclerosis Susceptibility Independently from HLA-DRB1*15:01
Cree BA, Rioux JD, McCauley JL, Gourraud PA, Goyette P, McElroy J, De Jager P, Santaniello A, Vyse TJ, Gregersen PK, Mirel D, Hafler DA, Haines JL, Pericak-Vance MA, Compston A, Sawcer SJ, Oksenberg JR, Hauser SL, , . A Major Histocompatibility Class I Locus Contributes to Multiple Sclerosis Susceptibility Independently from HLA-DRB1*15:01. PLOS ONE 2010, 5: e11296. PMID: 20593013, PMCID: PMC2892470, DOI: 10.1371/journal.pone.0011296.Peer-Reviewed Original ResearchConceptsCase-control analysisMS susceptibilityMultiple sclerosisSingle nucleotide polymorphismsClass IMS susceptibility allelesMultiple sclerosis susceptibilityMajor histocompatibility class ICochran-Armitage trend testLogistic regression modelingHLA-G geneMHC class IReplication datasetDiscovery datasetHistocompatibility class IArmitage trend testHLASignificant associationClass IIGenetic susceptibilityMajor histocompatibility complex (MHC) genesRegression modelingSusceptibility allelesP-valueMHCCIITA variation in the presence of HLA-DRB1*1501 increases risk for multiple sclerosis
Bronson PG, Caillier S, Ramsay PP, McCauley JL, Zuvich RL, De Jager PL, Rioux JD, Ivinson AJ, Compston A, Hafler DA, Sawcer SJ, Pericak-Vance MA, Haines JL, Consortium T, Hauser S, Oksenberg J, Barcellos L. CIITA variation in the presence of HLA-DRB1*1501 increases risk for multiple sclerosis. Human Molecular Genetics 2010, 19: 2331-2340. PMID: 20211854, PMCID: PMC2865376, DOI: 10.1093/hmg/ddq101.Peer-Reviewed Original ResearchConceptsClass II transactivator geneMultiple sclerosisPresence of HLAMHC class II transactivator geneMS risk alleleClass II MHCLogistic regression analysisG promoter variantPromoter variantsMS riskAntigen presentationII MHCIncrease riskRisk allelesMulti-stage investigationRs4774Important transcription factorSclerosisRegression analysisHLARiskStage 1Stage 2Transactivator geneAssociation
2009
Cathepsin S Regulates Class II MHC Processing in Human CD4+ HLA-DR+ T Cells
Costantino CM, Ploegh HL, Hafler DA. Cathepsin S Regulates Class II MHC Processing in Human CD4+ HLA-DR+ T Cells. The Journal Of Immunology 2009, 183: 945-952. PMID: 19553543, PMCID: PMC2752291, DOI: 10.4049/jimmunol.0900921.Peer-Reviewed Original ResearchConceptsT cellsCathepsin S expressionSelf-Ag presentationClass II MHC moleculesClass II MHCT cell clonesCathepsin SII MHC moleculesCLIP expressionProfessional APCsConsequence of activationII MHCHuman CD4Presentation pathwayB cellsMHC moleculesEx vivoHLACell clonesInvariant chain proteolysisLysosomal proteasesS expressionCellsActivationCell surfaceIL-17–producing human peripheral regulatory T cells retain suppressive function
Beriou G, Costantino CM, Ashley CW, Yang L, Kuchroo VK, Baecher-Allan C, Hafler DA. IL-17–producing human peripheral regulatory T cells retain suppressive function. Blood 2009, 113: 4240-4249. PMID: 19171879, PMCID: PMC2676084, DOI: 10.1182/blood-2008-10-183251.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, CDEnzyme-Linked Immunosorbent AssayFlow CytometryForkhead Transcription FactorsHLA-DR AntigensHumansImmune ToleranceInterleukin-17Interleukin-1betaInterleukin-6Lymphocyte ActivationReverse Transcriptase Polymerase Chain ReactionT-LymphocytesT-Lymphocytes, RegulatoryTransforming Growth Factor betaConceptsRegulatory T cellsIL-17Suppressive functionTreg clonesT cellsPeripheral regulatory T cellsProinflammatory cytokines IL-1betaSustained Foxp3 expressionIL-17 productionIL-17 secretionCytokines IL-1betaAutoimmune pathogenesisEffector cellsInterleukin-17Foxp3 expressionHuman TregsInflammatory milieuIL-6IL-1betaInflammatory conditionsImmune functionSuppressive activityTregsCellsRecent studies
2008
Integrating risk factors
De Jager PL, Simon KC, Munger KL, Rioux JD, Hafler DA, Ascherio A. Integrating risk factors. Neurology 2008, 70: 1113-1118. PMID: 18272866, DOI: 10.1212/01.wnl.0000294325.63006.f8.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntibodiesBiomarkersCase-Control StudiesComorbidityEpstein-Barr Virus InfectionsEpstein-Barr Virus Nuclear AntigensFemaleGene FrequencyGenetic Predisposition to DiseaseGenotypeHerpesvirus 4, HumanHeterozygoteHLA-DR AntigensHLA-DRB1 ChainsHumansMiddle AgedMultiple SclerosisRisk FactorsConceptsMultiple sclerosisHuman leukocyte antigenAntibody titersRisk factorsDR15 alleleEpstein-Barr virus (EBV) antibody titersAge-matched healthy womenRisk of MSEpstein-Barr virus nuclear antigen 1Independent risk factorVirus antibody titersCase-control studyNuclear antigen 1Healthy womenMS riskLeukocyte antigenRelative riskGenetic susceptibilityAntigen 1TitersWomenSclerosisRiskDR15Association
2007
Risk Alleles for Multiple Sclerosis Identified by a Genomewide Study
Hafler D, Compston A, Sawcer S, Lander E, Daly M, De Jager P, de Bakker P, Gabriel S, Mirel D, Ivinson A, Pericak-Vance M, Gregory S, Rioux J, McCauley J, Haines J, Barcellos L, Cree B, Oksenberg J, Hauser S. Risk Alleles for Multiple Sclerosis Identified by a Genomewide Study. New England Journal Of Medicine 2007, 357: 851-862. PMID: 17660530, DOI: 10.1056/nejmoa073493.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAllelesFemaleGenetic Predisposition to DiseaseGenome, HumanHLA-DR alpha-ChainsHLA-DR AntigensHumansInterleukin-2 Receptor alpha SubunitInterleukin-7 Receptor alpha SubunitLinkage DisequilibriumMaleMiddle AgedMultiple SclerosisMutationOligonucleotide Array Sequence AnalysisPolymorphism, Single NucleotideRisk FactorsConceptsMultiple sclerosisReceptor alpha geneSingle nucleotide polymorphismsControl subjectsCase subjectsInterleukin-7 receptor alpha geneHeritable risk factorsAlpha geneRisk factorsFamily triosSclerosisRisk allelesHLA lociHLA-DRA locusTransmission disequilibrium testStringent P valueP-valueEffect sizeSignificant heritable componentInterleukin-2 receptor alpha geneNonsynonymous single nucleotide polymorphismsGenomewide association studiesMultiple single nucleotide polymorphismsSubjectsAssociation
2006
MHC Class II Expression Identifies Functionally Distinct Human Regulatory T Cells
Baecher-Allan C, Wolf E, Hafler DA. MHC Class II Expression Identifies Functionally Distinct Human Regulatory T Cells. The Journal Of Immunology 2006, 176: 4622-4631. PMID: 16585553, DOI: 10.4049/jimmunol.176.8.4622.Peer-Reviewed Original ResearchConceptsContact-dependent suppressionRegulatory T cellsT cellsCD4 cellsDR expressionFunctional MHC class II moleculesRegulatory T cell populationHuman regulatory T cellsMHC class II determinantsIL-10 secretionClass II determinantsMHC class II moleculesHigh Foxp3 expressionMHC-II expressionEarly IL-4T cell populationsT cell nonresponsivenessClass II moleculesEx vivo expressionVivo expressionHuman CD4 cellsSubpopulations CD4Treg populationFoxp3 expressionIL-4
2005
Characterization of in vivo expanded OspA-specific human T-cell clones
Ausubel LJ, O'Connor KC, Baecher-Allen C, Trollmo C, Kessler B, Hekking B, Merritt D, Meyer AL, Kwok B, Ploegh H, Huber BT, Hafler DA. Characterization of in vivo expanded OspA-specific human T-cell clones. Clinical Immunology 2005, 115: 313-322. PMID: 15893699, DOI: 10.1016/j.clim.2005.02.015.Peer-Reviewed Original ResearchConceptsT cell clonesMajor histocompatibility complex class II tetramersTreatment-resistant Lyme arthritisCD4 T-cell clonesDistinct T-cell clonesT cell receptor repertoireHuman T cell clonesClass II tetramersBeta chainT cell recognitionTCR contact residuesTCR beta chainT cell receptorCell flow cytometryTCR usageImmune compartmentLyme arthritisAutoimmune diseasesMicrobial antigensT cellsOspA epitopeImmunodominant epitopesSynovial fluidReceptor repertoireReactive clonesExpanded T cells from pancreatic lymph nodes of type 1 diabetic subjects recognize an insulin epitope
Kent SC, Chen Y, Bregoli L, Clemmings SM, Kenyon NS, Ricordi C, Hering BJ, Hafler DA. Expanded T cells from pancreatic lymph nodes of type 1 diabetic subjects recognize an insulin epitope. Nature 2005, 435: 224-228. PMID: 15889096, DOI: 10.1038/nature03625.Peer-Reviewed Original ResearchConceptsWhite blood cellsAutoimmune diabetesLymph nodesType 1 diabetic subjectsPancreatic lymph nodesAntigen-specific therapyExpanded T cellsIslet cell transplantationType 1 diabetesPossible clinical relevanceStandard animal modelPrimary autoantigenNOD miceDiabetic subjectsImmune therapyMultiple sclerosisChildhood diabetesInsulin-producing cellsSpecific therapyImmune cellsT cellsT lymphocytesInsulin epitopesAnimal modelsClinical relevanceHigh 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
Cross-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
2001
CD4+CD25high Regulatory Cells in Human Peripheral Blood
Baecher-Allan C, Brown J, Freeman G, Hafler D. CD4+CD25high Regulatory Cells in Human Peripheral Blood. The Journal Of Immunology 2001, 167: 1245-1253. PMID: 11466340, DOI: 10.4049/jimmunol.167.3.1245.Peer-Reviewed Original ResearchMeSH KeywordsAbataceptAntigens, CDAntigens, DifferentiationB7-1 AntigenB7-H1 AntigenBlood ProteinsCD4 AntigensCD4-Positive T-LymphocytesCells, CulturedCoculture TechniquesCTLA-4 AntigenHLA-DR AntigensHumansImmunoconjugatesImmunosuppressive AgentsInterleukin-2KineticsLeukocyte Common AntigensLymphocyte ActivationLymphocyte CountMembrane GlycoproteinsPeptidesReceptors, Antigen, T-CellReceptors, Interleukin-2RNA, MessengerSignal TransductionT-Lymphocyte SubsetsConceptsRegulatory T cellsRegulatory cellsT cellsPD-1/PD-L1Regulatory CD4 T cellsAnti-CD3 stimulusCD4 T cellsHuman autoimmune disordersMultiorgan autoimmune diseasePeripheral lymphoid tissuesRegulatory cell functionIL-2 receptorPD-L1 receptorCirculation of humansHuman peripheral bloodContact-dependent mannerNeonatal day 3B7 pathwayPD-L1Regulatory populationAutoimmune disordersAutoimmune diseasesPeripheral bloodResponder cellsIL-2
2000
Human and Murine CD4 T Cell Reactivity to a Complex Antigen: Recognition of the Synthetic Random Polypeptide Glatiramer Acetate
Duda P, Krieger J, Schmied M, Balentine C, Hafler D. Human and Murine CD4 T Cell Reactivity to a Complex Antigen: Recognition of the Synthetic Random Polypeptide Glatiramer Acetate. The Journal Of Immunology 2000, 165: 7300-7307. PMID: 11120865, DOI: 10.4049/jimmunol.165.12.7300.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsCD4-Positive T-LymphocytesCell Line, TransformedCell SeparationClone CellsDose-Response Relationship, ImmunologicFemaleGlatiramer AcetateHematopoietic Stem CellsHLA-DR AntigensHumansImmunizationImmunologic MemoryImmunomagnetic SeparationInfant, NewbornLeukocytes, MononuclearLymphocyte ActivationLymphocyte CountMiceMice, Inbred BALB CMice, Inbred C57BLMultiple Sclerosis, Relapsing-RemittingPeptidesSpleenTh1 CellsTh2 CellsConceptsT cell populationsHLA class II DRGlatiramer acetateT cell proliferationClass II DRII DRT cellsCD4 T cell reactivityGA-reactive T cellsHuman T cell proliferative responsesT cell precursor frequencyCell populationsSpecific human T cell clonesT cell proliferative responsesHuman T cell clonesMemory T cellsT cell reactivityMultiple sclerosis patientsRecent clinical findingsCell precursor frequencyCell proliferative responsesCell proliferationT cell clonesDose-dependent proliferationHealthy human adultsDirect enumeration of Borrelia-reactive CD4 T cells ex vivo by using MHC class II tetramers
Meyer A, Trollmo C, Crawford F, Marrack P, Steere A, Huber B, Kappler J, Hafler D. Direct enumeration of Borrelia-reactive CD4 T cells ex vivo by using MHC class II tetramers. Proceedings Of The National Academy Of Sciences Of The United States Of America 2000, 97: 11433-11438. PMID: 11005833, PMCID: PMC17217, DOI: 10.1073/pnas.190335897.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, SurfaceBacterial Outer Membrane ProteinsBacterial VaccinesBiopolymersBorrelia burgdorferi GroupCD4-Positive T-LymphocytesClone CellsCytokinesDose-Response Relationship, ImmunologicHLA-DR AntigensHLA-DRB1 ChainsHumansIn Vitro TechniquesLipoproteinsLyme DiseaseLyme Disease VaccinesConceptsClass II tetramersMHC class II tetramersT cellsSynovial fluidPeripheral bloodMajor histocompatibility complex class II tetramersTreatment-resistant Lyme arthritisAntigen-reactive T cellsCD4 T cellsDifferent cytokine profilesIL-13 secretionT cell clonesAllogeneic feeder cellsCytokine profileLyme arthritisInflammatory compartmentIL-2IFN-gammaImmunodominant epitopesCell clonesBorrelia burgdorferiPatientsHLABloodCells
1996
Complementary mutations in an antigenic peptide allow for crossreactivity of autoreactive T-cell clones
Ausubel L, Kwan C, Sette A, Kuchroo V, Hafler D. Complementary mutations in an antigenic peptide allow for crossreactivity of autoreactive T-cell clones. Proceedings Of The National Academy Of Sciences Of The United States Of America 1996, 93: 15317-15322. PMID: 8986809, PMCID: PMC26402, DOI: 10.1073/pnas.93.26.15317.Peer-Reviewed Original ResearchConceptsT cell clonesT cell receptorAutoreactive T cell clonesSpecific T cell clonesAntigenic peptidesMajor histocompatibility complex moleculesSpecific peptide antigenContext of MHCT cell recognitionTCR contact residuesMHC-antigen complexesHistocompatibility complex moleculesMHC-peptide complexesSingle conservative amino acid substitutionTCR-MHCT cellsReceptor plasticityPeptide antigensFunctional pocketStimulating peptideCrossreactivityAntigenTrimolecular complexAmino acid substitutionsConservative amino acid substitutionsActivation of human T cell lymphotropic virus type I-infected T cells is independent of B7 costimulation.
Scholz C, Freeman GJ, Greenfield EA, Hafler DA, Höllsberg P. Activation of human T cell lymphotropic virus type I-infected T cells is independent of B7 costimulation. The Journal Of Immunology 1996, 157: 2932-8. PMID: 8816399, DOI: 10.4049/jimmunol.157.7.2932.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalAntigen-Presenting CellsAntigens, CDAutoimmunityB7-1 AntigenB7-2 AntigenBase SequenceCD28 AntigensCHO CellsClone CellsCricetinaeCricetulusEnzyme ActivationHLA-DR AntigensHLA-DRB1 ChainsHuman T-lymphotropic virus 1HumansInterferon-gammaInterleukin-4Interleukin-5Janus Kinase 3Lymphocyte ActivationMembrane GlycoproteinsMolecular Sequence DataMyelin Basic ProteinProtein-Tyrosine KinasesSignal TransductionT-Lymphocyte SubsetsTransfectionConceptsHuman T-cell lymphotropic virus type ILymphotropic virus type IB7 costimulationT cell clonesT cellsB7-1Virus type IIL-4IL-5B7-2IFN-gammaAutoreactive T cell responsesCell clonesAg-specific signalAutoimmune-like diseaseT cell responsesAutoreactive T cellsHTLV-I infectionB7-2 costimulationB7-2 moleculesUninfected T cellsType IAutoimmune responseB7 expressionCytokine secretion
1994
Clonal 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 sequences