2021
Circulating clonally expanded T cells reflect functions of tumor-infiltrating T cells
Lucca LE, Axisa PP, Lu B, Harnett B, Jessel S, Zhang L, Raddassi K, Zhang L, Olino K, Clune J, Singer M, Kluger HM, Hafler DA. Circulating clonally expanded T cells reflect functions of tumor-infiltrating T cells. Journal Of Experimental Medicine 2021, 218: e20200921. PMID: 33651881, PMCID: PMC7933991, DOI: 10.1084/jem.20200921.Peer-Reviewed Original ResearchMeSH KeywordsClone CellsCytotoxicity, ImmunologicHumansImmunotherapyLymphocytes, Tumor-InfiltratingMelanomaMonitoring, ImmunologicNeoplasm MetastasisPhenotypeReceptors, Antigen, T-Cell, alpha-betaSkin NeoplasmsT-Lymphocytes, CytotoxicTranscriptomeConceptsTumor-infiltrating T cellsT cellsUnique transcriptional patternsFeatures of exhaustionLongitudinal immune monitoringPeripheral immune environmentsT cell responsesT cell functionSingle-cell levelTranscriptional patternsTCR sharingTerminal exhaustionImmune environmentImmune monitoringCancer immunotherapyMetastatic melanomaEffector functionsCell responsesTumor tissueGene signatureTumorsCell functionImmunotherapyTCRαβBlood
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
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
Conserved CDR3 Regions in T-Cell Receptor (TCR) CD8+T Cells That Recognize the Tax11-19/HLA-A*0201 Complex in a Subject Infected with Human T-Cell Leukemia Virus Type 1: Relationship of T-Cell Fine Specificity and Major Histocompatibility Complex/Peptide/TCR Crystal Structure
Bourcier K, Lim D, Ding Y, Smith K, Wucherpfennig K, Hafler D. Conserved CDR3 Regions in T-Cell Receptor (TCR) CD8+T Cells That Recognize the Tax11-19/HLA-A*0201 Complex in a Subject Infected with Human T-Cell Leukemia Virus Type 1: Relationship of T-Cell Fine Specificity and Major Histocompatibility Complex/Peptide/TCR Crystal Structure. Journal Of Virology 2001, 75: 9836-9843. PMID: 11559817, PMCID: PMC114556, DOI: 10.1128/jvi.75.20.9836-9843.2001.Peer-Reviewed Original ResearchConceptsT cell clonesT cell receptorCDR3 regionTCR alphaHTLV-1-associated myelopathyTax11-19Beta chainHTLV-1-infected individualsT cell receptor repertoirePeripheral blood lymphocytesHuman T-cell leukemia virusHuman T-cell leukemia virus type 1T-cell leukemia virusVirus type 1TCR usageT cell fine specificityBlood lymphocytesT cellsImmunodominant epitopesReceptor repertoireType 1Fine specificitySimilar recognition patternTCR structureLeukemia virus
2000
Multiple differences in gene expression in regulatory Vα24JαQ T cells from identical twins discordant for type I diabetes
Wilson S, Kent S, Horton H, Hill A, Bollyky P, Hafler D, Strominger J, Byrne M. Multiple differences in gene expression in regulatory Vα24JαQ T cells from identical twins discordant for type I diabetes. Proceedings Of The National Academy Of Sciences Of The United States Of America 2000, 97: 7411-7416. PMID: 10840051, PMCID: PMC16559, DOI: 10.1073/pnas.120161297.Peer-Reviewed Original ResearchMeSH KeywordsDiabetes Mellitus, Type 1Gene Expression RegulationHumansImmunoglobulin Variable RegionReceptors, Antigen, T-Cell, alpha-betaT-LymphocytesTwinsConceptsT cell receptor activationCell receptor activationT cellsTranscriptional consequencesDNA microarraysGene expressionActivation of cellsMyeloid lineageClonesMurine autoimmune diseaseInvariant T (MAIT) cellsIL-4 secretionType 1 diabetesAnti-CD3 stimulationT cell clonesIdentical twinsMRNA levelsReceptor activationCellsCell clonesAutoimmune diseasesActivationSecreting clonesQualitative defectsMultiple differences
1999
Noncanonical Vα24JαQ T cells with conservative α chain CDR3 region amino acid substitutions are restricted by CD1d
Kent S, Hafler D, Strominger J, Wilson S. Noncanonical Vα24JαQ T cells with conservative α chain CDR3 region amino acid substitutions are restricted by CD1d. Human Immunology 1999, 60: 1080-1089. PMID: 10600006, DOI: 10.1016/s0198-8859(99)00109-3.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAntigens, CD1Antigens, CD1dBase SequenceClone CellsComplementarity Determining RegionsConserved SequenceDNAGene Rearrangement, alpha-Chain T-Cell Antigen ReceptorHumansImmunoglobulin Variable RegionImmunophenotypingKiller Cells, NaturalReceptors, Antigen, T-Cell, alpha-betaT-Lymphocyte SubsetsConceptsT cell receptorT cellsCD1d restrictionPeripheral blood mononuclear cellsBlood mononuclear cellsAmino acid substitutionsAlpha chainSingle amino acid substitutionHuman CD161Total CD4Mononuclear cellsInterleukin-4Surface phenotypeRestriction elementsCD4Acid substitutionsCD1dCDR3 residuesJ rearrangementsJ junctionsVariant clonesChain transcriptsCellsJalpha18Valpha24Differential responses of invariant V alpha 24J alpha Q T cells and MHC class II-restricted CD4+ T cells to dexamethasone.
Milner J, Kent S, Ashley T, Wilson S, Strominger J, Hafler D. Differential responses of invariant V alpha 24J alpha Q T cells and MHC class II-restricted CD4+ T cells to dexamethasone. The Journal Of Immunology 1999, 163: 2522-9. PMID: 10452989, DOI: 10.4049/jimmunol.163.5.2522.Peer-Reviewed Original ResearchMeSH KeywordsAdjuvants, ImmunologicAntibodies, BlockingAntibodies, MonoclonalAntigens, CD1Antigens, CD1dAntigens, Differentiation, B-LymphocyteApoptosisAutocrine CommunicationCD3 ComplexCD4-Positive T-LymphocytesClone CellsDexamethasoneDose-Response Relationship, ImmunologicFas ReceptorHistocompatibility Antigens Class IIHumansImmunosuppressive AgentsInterleukin-2Lymphocyte ActivationReceptors, Antigen, T-Cell, alpha-betaSignal TransductionT-Lymphocyte SubsetsConceptsActivation-induced cell deathT cell clonesT cellsTCR signal strengthCell clonesAutocrine IL-2 productionNK T cellsT cell responsesT cell subsetsInhibition of CD4Anti-CD3 stimulationT cell proliferationEffect of dexamethasoneMHC class IIIL-2 productionPresence of dexamethasoneExogenous corticosteroidsCell subsetsImmunomodulatory consequencesDexamethasone treatmentImmune responseCD4High dosesLow dosesCell responsesCross-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 ResearchMeSH KeywordsAmino Acid SequenceCell LineCross ReactionsHumansMolecular Sequence DataMyelin Basic ProteinPeptide FragmentsReceptors, Antigen, T-Cell, alpha-betaT-LymphocytesConceptsT 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 reactivityDirect analysis of viral-specific CD8+ T cells with soluble HLA-A2/Tax11-19 tetramer complexes in patients with human T cell lymphotropic virus-associated myelopathy.
Bieganowska K, Höllsberg P, Buckle G, Lim D, Greten T, Schneck J, Altman J, Jacobson S, Ledis S, Hanchard B, Chin J, Morgan O, Roth P, Hafler D. Direct analysis of viral-specific CD8+ T cells with soluble HLA-A2/Tax11-19 tetramer complexes in patients with human T cell lymphotropic virus-associated myelopathy. The Journal Of Immunology 1999, 162: 1765-71. PMID: 9973440, DOI: 10.4049/jimmunol.162.3.1765.Peer-Reviewed Original ResearchMeSH KeywordsAdultB7-1 AntigenCD28 AntigensCD8-Positive T-LymphocytesFemaleGene Products, taxHLA-A2 AntigenHuman T-lymphotropic virus 1HumansLymphocyte ActivationMaleMiddle AgedParaparesis, Tropical SpasticPeptide FragmentsPhenotypeProtein ConformationReceptors, Antigen, T-Cell, alpha-betaReceptors, ChemokineReceptors, Interleukin-2SolubilityConceptsT cellsIL-2RMHC class I tetramersHuman T-cell lymphotropic virusViral-specific CD8Class I tetramersProgressive neurologic diseaseDifferent chemokine receptorsHLA-A2 alleleCentral nervous systemTCR Vbeta chainsReactive CD8TCR usageInflammatory infiltrateVbeta chainsChemokine receptorsNeurologic diseaseImmune responseCD8Lymphotropic virusMyelopathyNervous systemPatientsHTLVClonal expansion
1997
Changes in cytokine secretion induced by altered peptide ligands of myelin basic protein peptide 85-99.
Ausubel LJ, Krieger JI, Hafler DA. Changes in cytokine secretion induced by altered peptide ligands of myelin basic protein peptide 85-99. The Journal Of Immunology 1997, 159: 2502-12. PMID: 9278344, DOI: 10.4049/jimmunol.159.5.2502.Peer-Reviewed Original ResearchAutoimmune DiseasesCell DifferentiationCell LineClone CellsGene Rearrangement, T-LymphocyteHumansImmunodominant EpitopesInterferon-gammaInterleukin-4Interleukin-5Lymphocyte ActivationMultiple SclerosisMyelin Basic ProteinPeptide FragmentsReceptors, Antigen, T-Cell, alpha-betaStructure-Activity RelationshipT-Lymphocyte SubsetsTh1 CellsTh2 CellsDirect 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
TCR usage in human and experimental demyelinating disease
Hafler D, Saadeh M, Kuchroo V, Milford E, Steinman L. TCR usage in human and experimental demyelinating disease. Trends In Immunology 1996, 17: 152-159. PMID: 8871344, DOI: 10.1016/0167-5699(96)80611-6.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsConserved SequenceDemyelinating DiseasesEncephalomyelitis, Autoimmune, ExperimentalHumansMultiple SclerosisReceptors, Antigen, T-Cell, alpha-beta
1995
Structure of human T-cell receptors specific for an immunodominant myelin basic protein peptide: positioning of T-cell receptors on HLA-DR2/peptide complexes.
Wucherpfennig KW, Hafler DA, Strominger JL. Structure of human T-cell receptors specific for an immunodominant myelin basic protein peptide: positioning of T-cell receptors on HLA-DR2/peptide complexes. Proceedings Of The National Academy Of Sciences Of The United States Of America 1995, 92: 8896-8900. PMID: 7568039, PMCID: PMC41074, DOI: 10.1073/pnas.92.19.8896.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
Functional three-domain single-chain T-cell receptors.
Chung S, Wucherpfennig KW, Friedman SM, Hafler DA, Strominger JL. Functional three-domain single-chain T-cell receptors. Proceedings Of The National Academy Of Sciences Of The United States Of America 1994, 91: 12654-12658. PMID: 7809095, PMCID: PMC45497, DOI: 10.1073/pnas.91.26.12654.Peer-Reviewed Original ResearchClonal 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 ResearchMeSH KeywordsAdultAmino Acid SequenceBase SequenceCell LineFemaleHLA-DR AntigensHumansInterleukin-2MaleMiddle AgedMolecular Sequence DataMyelin Basic ProteinPeptide FragmentsReceptors, Antigen, T-Cell, alpha-betaT-LymphocytesConceptsT 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 ResearchMeSH KeywordsAmino Acid SequenceAnimalsBase SequenceDisease SusceptibilityDNAEncephalomyelitis, Autoimmune, ExperimentalMiceMice, TransgenicMolecular Sequence DataReceptors, Antigen, T-CellReceptors, Antigen, T-Cell, alpha-betaConceptsExperimental 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
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 ResearchMeSH KeywordsAdultCD4 AntigensCD8 AntigensCell LineEpitopesFemaleHumansImmunotherapy, AdoptiveLymphocyte ActivationMaleMiddle AgedMultiple SclerosisMyelin Basic ProteinReceptors, Antigen, T-Cell, alpha-betaT-LymphocytesVaccinationConceptsAutoreactive 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
1992
T cell receptor V alpha-V beta repertoire and cytokine gene expression in active multiple sclerosis lesions.
Wucherpfennig KW, Newcombe J, Li H, Keddy C, Cuzner ML, Hafler DA. T cell receptor V alpha-V beta repertoire and cytokine gene expression in active multiple sclerosis lesions. Journal Of Experimental Medicine 1992, 175: 993-1002. PMID: 1348083, PMCID: PMC2119186, DOI: 10.1084/jem.175.4.993.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAntigens, Differentiation, T-LymphocyteBase SequenceCD2 AntigensChronic DiseaseClone CellsCytokinesGene ExpressionHumansInterleukin-1Interleukin-2Interleukin-4Molecular Sequence DataMultiple SclerosisOligodeoxyribonucleotidesPolymerase Chain ReactionReceptors, Antigen, T-Cell, alpha-betaReceptors, ImmunologicRNA, MessengerConceptsTCR V alphaTCR repertoireBeta repertoireMultiple sclerosisV alphaActive lesionsMS plaquesT cellsAlpha/beta T cellsActive multiple sclerosis lesionsMS plaque tissueCentral nervous system tissueT cell recruitmentBeta T cellsActive MS plaquesChronic inflammatory diseaseIL-4 mRNAT cell expansionIL-1 mRNATCR V gene segmentsCentral nervous systemCases of subacuteNervous system tissueSites of inflammationTCR V genes
1990
Shared 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