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 ResearchConceptsTumor-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
2014
B cells populating the multiple sclerosis brain mature in the draining cervical lymph nodes
Stern JN, Yaari G, Vander Heiden JA, Church G, Donahue WF, Hintzen RQ, Huttner AJ, Laman JD, Nagra RM, Nylander A, Pitt D, Ramanan S, Siddiqui BA, Vigneault F, Kleinstein SH, Hafler DA, O'Connor KC. B cells populating the multiple sclerosis brain mature in the draining cervical lymph nodes. Science Translational Medicine 2014, 6: 248ra107. PMID: 25100741, PMCID: PMC4388137, DOI: 10.1126/scitranslmed.3008879.Peer-Reviewed Original ResearchConceptsCervical lymph nodesCentral nervous systemB cellsCerebrospinal fluidLymph nodesMultiple sclerosisLymphoid tissueCNS of patientsCNS B cellsAntigen-experienced B cellsMultiple sclerosis brainSecondary lymphoid tissuesB cell compartmentB cell trafficB cell maturationImmunomodulatory therapyImmune infiltratesPeripheral bloodInflammatory diseasesLymphocyte transmigrationPeripheral tissuesNervous systemMembers of clonesCell maturationCell traffic
2011
Related B cell clones that populate the CSF and CNS of patients with multiple sclerosis produce CSF immunoglobulin
Obermeier B, Lovato L, Mentele R, Brück W, Forne I, Imhof A, Lottspeich F, Turk KW, Willis SN, Wekerle H, Hohlfeld R, Hafler DA, O'Connor KC, Dornmair K. Related B cell clones that populate the CSF and CNS of patients with multiple sclerosis produce CSF immunoglobulin. Journal Of Neuroimmunology 2011, 233: 245-248. PMID: 21353315, PMCID: PMC3090654, DOI: 10.1016/j.jneuroim.2011.01.010.Peer-Reviewed Original ResearchRelated B cell clones populate the meninges and parenchyma of patients with multiple sclerosis
Lovato L, Willis SN, Rodig SJ, Caron T, Almendinger SE, Howell OW, Reynolds R, O’Connor K, Hafler DA. Related B cell clones populate the meninges and parenchyma of patients with multiple sclerosis. Brain 2011, 134: 534-541. PMID: 21216828, PMCID: PMC3030766, DOI: 10.1093/brain/awq350.Peer-Reviewed Original ResearchConceptsB cell clonesB cell aggregatesMultiple sclerosisCentral nervous systemParenchymal infiltratesCell clonesNervous systemMeningeal B cell aggregatesRelated B cell clonesProgressive multiple sclerosisB-cell infiltratesCerebral spinal fluidInflammatory plaquesCell infiltrateImmune compartmentParenchymal lesionsLymphoid tissueSclerosisSpinal fluidWhite matterPatientsGray matterBrain tissueInfiltratesMeninges
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 cellsCathepsin 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 surface
2008
Lysosomal Cysteine and Aspartic Proteases Are Heterogeneously Expressed and Act Redundantly to Initiate Human Invariant Chain Degradation
Costantino CM, Hang HC, Kent SC, Hafler DA, Ploegh HL. Lysosomal Cysteine and Aspartic Proteases Are Heterogeneously Expressed and Act Redundantly to Initiate Human Invariant Chain Degradation. The Journal Of Immunology 2008, 180: 2876-2885. PMID: 18292509, DOI: 10.4049/jimmunol.180.5.2876.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAntigen PresentationAntigens, Differentiation, B-LymphocyteAspartic Acid EndopeptidasesB-LymphocytesCD4-Positive T-LymphocytesCell Line, TransformedClone CellsCoculture TechniquesCysteine EndopeptidasesGene Expression Regulation, EnzymologicGenetic HeterogeneityHistocompatibility Antigens Class IIHLA-D AntigensHumansLysosomesMolecular Sequence DataProtease InhibitorsProtein Processing, Post-TranslationalConceptsAsparagine endopeptidasePeptide AgClass II MHC productsMyelin basic protein epitopeClass II MHCClass II invariant chainInvariant chain cleavageInvariant chain degradationPresentation of AgInvariant chain processingAEP inhibitionB cell linesDistinct allelic variantsII MHCMHC productsDifferent EBVMHC dimersAllelic variantsHuman AgInvariant chainAltered regulation
2007
Multispecific responses by T cells expanded by endogenous self‐peptide/MHC complexes
Cai G, Hafler DA. Multispecific responses by T cells expanded by endogenous self‐peptide/MHC complexes. European Journal Of Immunology 2007, 37: 602-612. PMID: 17304631, DOI: 10.1002/eji.200636787.Peer-Reviewed Original ResearchConceptsT cellsHuman T cell responsesSelf-peptide/MHCSelf-peptide/MHC complexesEndogenous self-antigenPercentage of CD4Pathological immune responsesT cell responsesAntigen-presenting cellsT cell clonesCell cycleMultispecific responseMHC determinantsSelf antigensAntigen stimulationHealthy subjectsImmune responseAntigen reactivityCD4Cell responsesMultiple antigensCD28 costimulationMHC complexesCell clonesTCRbeta chain
2006
Dysregulated T cell expression of TIM3 in multiple sclerosis
Koguchi K, Anderson DE, Yang L, O'Connor KC, Kuchroo VK, Hafler DA. Dysregulated T cell expression of TIM3 in multiple sclerosis. Journal Of Experimental Medicine 2006, 203: 1413-1418. PMID: 16754722, PMCID: PMC2118310, DOI: 10.1084/jem.20060210.Peer-Reviewed Original ResearchConceptsIFN-gamma secretionCSF clonesT cell expressionMultiple sclerosisT cellsHuman T cellsTIM3 expressionControl subjectsCerebrospinal fluidCell expressionMucin-domain-containing moleculesPathogenesis of MSEx vivo CD4Human autoimmune diseasesT helper cellsT-cell immunoglobulinT cell clonesVivo CD4Costimulatory blockadeTh1 responseCytokine profileCell surface moleculesAutoimmune diseasesHelper cellsInterleukin-12
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 relevance
2002
Strength of prior stimuli determines the magnitude of secondary responsiveness in CD8+ T cells
Lim DG, Höllsberg P, Hafler DA. Strength of prior stimuli determines the magnitude of secondary responsiveness in CD8+ T cells. Cellular Immunology 2002, 217: 36-46. PMID: 12425999, DOI: 10.1016/s0008-8749(02)00511-7.Peer-Reviewed Original ResearchConceptsT cellsSecondary responsivenessCostimulatory moleculesInduction of CD8Magnitude of CD8T cell responsesT cell anergyCell anergyCD8Prior stimulusSecondary stimulationPrimary stimulationCell responsesCellular mechanismsFollowing activationPeptide ligandsActivation thresholdStimulationCellsResponsivenessHigh levelsCD4AnergyStimuliStrength of signal
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 virusIn vitro evidence that immunuaffinity-purified MOG contains immunogenic quantities of contaminating mouse IgG; techniques for producing Ig-free MOG
Ohashi T, Yukitake M, Slavin A, Krieger J, Hafler D. In vitro evidence that immunuaffinity-purified MOG contains immunogenic quantities of contaminating mouse IgG; techniques for producing Ig-free MOG. Journal Of Neuroimmunology 2001, 118: 194-202. PMID: 11498254, DOI: 10.1016/s0165-5728(01)00321-6.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalAntibody SpecificityBlotting, WesternCell LineClone CellsCytokinesElectrophoresis, Polyacrylamide GelEnzyme-Linked Immunosorbent AssayFlow CytometryHumansImmunoglobulin GImmunophenotypingImmunosorbent TechniquesLymphocyte ActivationMiceMultiple SclerosisMyelin ProteinsMyelin SheathMyelin-Associated GlycoproteinMyelin-Oligodendrocyte GlycoproteinSensitivity and SpecificityT-LymphocytesMolecular Mimicry in Lyme Arthritis Demonstrated at the Single Cell Level: LFA-1αL Is a Partial Agonist for Outer Surface Protein A-Reactive T Cells
Trollmo C, Meyer A, Steere A, Hafler D, Huber B. Molecular Mimicry in Lyme Arthritis Demonstrated at the Single Cell Level: LFA-1αL Is a Partial Agonist for Outer Surface Protein A-Reactive T Cells. The Journal Of Immunology 2001, 166: 5286-5291. PMID: 11290815, DOI: 10.4049/jimmunol.166.8.5286.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, SurfaceBacterial Outer Membrane ProteinsBacterial VaccinesBorrelia burgdorferi GroupClone CellsHumansHybridomasLipoproteinsLyme DiseaseLyme Disease VaccinesLymphocyte ActivationLymphocyte Function-Associated Antigen-1MiceMice, TransgenicMolecular MimicryPeptide FragmentsT-Lymphocyte SubsetsConceptsIL-13Antibiotic treatment-resistant Lyme arthritisPartial agonistTreatment-resistant Lyme arthritisChronic inflammatory joint diseaseT cell hybridsDR4 transgenic miceHuman T cell clonesClass II tetramersInflammatory joint diseaseSymptoms of arthritisT cell responsesT cell levelsEpisodes of arthritisT cell clonesSurface protein AAutoimmune mechanismsOuter surface protein ALyme arthritisJoint diseaseT cellsIFN-gammaImmunodominant epitopesCell levelTransgenic miceUncoupling p70s6 Kinase Activation and Proliferation: Rapamycin-Resistant Proliferation of Human CD8+ T Lymphocytes
Slavik J, Lim D, Burakoff S, Hafler D. Uncoupling p70s6 Kinase Activation and Proliferation: Rapamycin-Resistant Proliferation of Human CD8+ T Lymphocytes. The Journal Of Immunology 2001, 166: 3201-3209. PMID: 11207273, DOI: 10.4049/jimmunol.166.5.3201.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalCD2 AntigensCD28 AntigensCD3 ComplexCD8 AntigensCD8-Positive T-LymphocytesCell Line, TransformedClone CellsDose-Response Relationship, DrugDose-Response Relationship, ImmunologicDrug ResistanceEnzyme ActivationEpitopes, T-LymphocyteHLA-A AntigensHumansImmunosuppressive AgentsInterleukin-2Lymphocyte ActivationMajor Histocompatibility ComplexModels, ImmunologicalRibosomal Protein S6 KinasesSirolimusT-Lymphocyte SubsetsConceptsT cell clonesT cellsEffect of rapamycinHuman T cell responsesPeripheral blood T cellsCell clonesHeterogeneous proliferative responsesT cell responsesBlood T cellsT cell proliferationSpecific costimulatory signalsGraft infiltrationResistant proliferationInhibition of AgGraft rejectionHuman CD8IL-2RT lymphocytesProliferative responseCostimulatory signalsCell responsesPresence of rapamycinCell proliferationRapamycinProliferationDecreases in Interleukin-4 Secretion by Invariant CD4−CD8−Vα24JαQ T Cells in Peripheral Blood of Patients with Relapsing–Remitting Multiple Sclerosis
Gausling R, Trollmo C, Hafler D. Decreases in Interleukin-4 Secretion by Invariant CD4−CD8−Vα24JαQ T Cells in Peripheral Blood of Patients with Relapsing–Remitting Multiple Sclerosis. Clinical Immunology 2001, 98: 11-17. PMID: 11141321, DOI: 10.1006/clim.2000.4942.Peer-Reviewed Original ResearchConceptsRelapsing-remitting multiple sclerosisT cell receptorIFN-gamma secretionMultiple sclerosisT cell clonesT cellsCytokine profilePeripheral bloodIL-4Cell clonesProgressive multiple sclerosisRR-MS patientsCytokine secretion patternsRelapsing-remitting MSInterleukin-4 secretionT cell functionalityCytokine secretionHealthy controlsSecretion patternPatientsCP-MSImmune systemControl individualsCell receptorSecretion
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 adultsExamination of CD8+ T Cell Function in Humans Using MHC Class I Tetramers: Similar Cytotoxicity but Variable Proliferation and Cytokine Production Among Different Clonal CD8+ T Cells Specific to a Single Viral Epitope
Lim D, Bourcier K, Freeman G, Hafler D. Examination of CD8+ T Cell Function in Humans Using MHC Class I Tetramers: Similar Cytotoxicity but Variable Proliferation and Cytokine Production Among Different Clonal CD8+ T Cells Specific to a Single Viral Epitope. The Journal Of Immunology 2000, 165: 6214-6220. PMID: 11086055, DOI: 10.4049/jimmunol.165.11.6214.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, ViralB7-1 AntigenCD58 AntigensCD8-Positive T-LymphocytesCell Line, TransformedClone CellsCytokinesCytotoxicity, ImmunologicDose-Response Relationship, ImmunologicEpitopes, T-LymphocyteGene Products, taxGenes, T-Cell Receptor betaHLA-A2 AntigenHuman T-lymphotropic virus 1HumansLymphocyte ActivationPeptide FragmentsStaining and LabelingConceptsT cell clonesCytokine secretionT cellsEffector functionsCell clonesCostimulatory moleculesViral epitopesHuman T-cell lymphotrophic virusDifferent T cell clonesImmunodominant viral epitopesCytotoxic effector functionClonal originT cell functionSingle viral epitopeMHC class IDifferent clonal originCD2-LFA-3 interactionInduction of proliferationClonal CD8Cytokine productionPeripheral bloodCTL populationsIL-2Lymphotrophic virusProliferative responseDirect 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