2021
Single cell immunophenotyping of the skin lesion erythema migrans Identifies IgM memory B cells
Jiang R, Meng H, Raddassi K, Fleming I, Hoehn KB, Dardick KR, Belperron AA, Montgomery RR, Shalek AK, Hafler DA, Kleinstein SH, Bockenstedt LK. Single cell immunophenotyping of the skin lesion erythema migrans Identifies IgM memory B cells. JCI Insight 2021, 6: e148035. PMID: 34061047, PMCID: PMC8262471, DOI: 10.1172/jci.insight.148035.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedB-LymphocytesErythema Chronicum MigransFemaleHistocompatibility Antigens Class IIHumansImmunoglobulin MImmunophenotypingLyme DiseaseMaleMiddle AgedRNA-SeqSingle-Cell AnalysisSkinTranscriptomeConceptsMemory B cellsErythema migransB cellsEM lesionsIgM memory B cellsLyme diseaseB-cell receptor sequencingSkin infection siteCell receptor sequencingEarly Lyme diseaseLocal antigen presentationSkin immune responsesB cell populationsSingle-cell immunophenotypingMHC class II genesUninvolved skinImmune cellsSpirochetal infectionAntigen presentationCell immunophenotypingT cellsImmune responseIsotype usageAntibody productionInitial signs
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
2009
On-Chip Activation and Subsequent Detection of Individual Antigen-Specific T Cells
Song Q, Han Q, Bradshaw EM, Kent SC, Raddassi K, Nilsson B, Nepom GT, Hafler DA, Love JC. On-Chip Activation and Subsequent Detection of Individual Antigen-Specific T Cells. Analytical Chemistry 2009, 82: 473-477. PMID: 20000848, PMCID: PMC2828941, DOI: 10.1021/ac9024363.Peer-Reviewed Original ResearchMeSH KeywordsAntibodiesCD4-Positive T-LymphocytesHistocompatibility Antigens Class IIHumansInterferon-gammaInterleukin-17Lab-On-A-Chip DevicesPeptidesTissue Array AnalysisConceptsAntigen-specific T cellsAntigen-specific CD4T cellsAntigen-specific mannerType 1 diabetesMajor histocompatibility complex receptorIndividual CD4Multiple sclerosisAutoimmune diseasesPrimary T cellsCD4Subnanoliter wellsClinical samplesNumber of cellsComplex receptorSubsequent assessmentHuman tissuesCellsChip activationVivoActivationSclerosisDiabetesCytokinesDiseaseEvaluating the Intrinsic Cysteine Redox-Dependent States of the A-Chain of Human Insulin Using NMR Spectroscopy, Quantum Chemical Calculations, and Mass Spectrometry
Sharma AK, Ling Y, Greer AB, Hafler DA, Kent SC, Zhang Y, Rigby AC. Evaluating the Intrinsic Cysteine Redox-Dependent States of the A-Chain of Human Insulin Using NMR Spectroscopy, Quantum Chemical Calculations, and Mass Spectrometry. The Journal Of Physical Chemistry B 2009, 114: 585-591. PMID: 19954153, PMCID: PMC2829747, DOI: 10.1021/jp908729h.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceCysteineHistocompatibility Antigens Class IIHumansInsulinMagnetic Resonance SpectroscopyMass SpectrometryMolecular Sequence DataOxidation-ReductionQuantum TheoryConceptsQuantum chemical calculationsChemical calculationsFree thiol moietyNMR spectroscopy dataA-chain peptideRedox chemistryNMR spectroscopyThiol moietyCell surface class II moleculesMass spectrometry analysisOxidized stateFunctional studiesA-chain analogueIntrinsic cysteine residuesMass spectrometryPeptide interactionsConformational equilibriumSpectroscopy dataRedox-dependent mechanismDisulfide conformationSpectrometry analysisDependent conformational equilibriumPrevious functional studiesConformationProtein systemsCathepsin 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
Human regulatory T cells and autoimmunity
Costantino CM, Baecher‐Allan C, Hafler DA. Human regulatory T cells and autoimmunity. European Journal Of Immunology 2008, 38: 921-924. PMID: 18395861, PMCID: PMC2752283, DOI: 10.1002/eji.200738104.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutoimmune DiseasesAutoimmunityCell MembraneHistocompatibility Antigens Class IIHumansSignal TransductionT-Lymphocytes, RegulatoryLysosomal 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
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
1999
Differential 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 responses
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
1994
T cell anergy
Lasalle J, Hafler D. T cell anergy. The FASEB Journal 1994, 8: 601-608. PMID: 8005388, DOI: 10.1096/fasebj.8.9.8005388.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigen PresentationAutoantigensHistocompatibility Antigens Class IIHumansImmune ToleranceInflammationT-LymphocytesConceptsImmunologic self toleranceAutoreactive T cellsT cell anergyMHC class IIT cellsClonal anergyT cell presentationT cell clonal anergySelf antigensCell anergySelf toleranceCell presentationClass IIAutologous T cellsAbsence of costimulationHuman T cellsSecondary unresponsivenessHigh extracellular concentrationsAntigenic stimulationAntigen presentationAntigen resultsAnergyPrimary proliferationPeptide antigensAntigen
1993
T-cell presentation of antigen requires cell-to-cell contact for proliferation and anergy induction. Differential MHC requirements for superantigen and autoantigen.
LaSalle JM, Toneguzzo F, Saadeh M, Golan DE, Taber R, Hafler DA. T-cell presentation of antigen requires cell-to-cell contact for proliferation and anergy induction. Differential MHC requirements for superantigen and autoantigen. The Journal Of Immunology 1993, 151: 649-57. PMID: 7687620, DOI: 10.4049/jimmunol.151.2.649.Peer-Reviewed Original ResearchConceptsStaphylococcal enterotoxin BT cell clonesT cellsT cell presentationAnergy inductionCalcium fluxMHC classCell contactHuman T cell clonesCell interactionsT cell coculturesT cell responsesMHC class IIT cell interactionsT cell migrationIndividual T cellsSingle T cellsSubsequent anergyHLA-DRIndividual CD4Class IIAnergyEnterotoxin BSuperantigensSelf-Stimulation
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 ResearchMeSH KeywordsAntigens, Differentiation, T-LymphocyteDNAEpitopesHerpes ZosterHerpesvirus 3, HumanHistocompatibility Antigens Class IIHumansMaleMeningoencephalitisMiddle AgedNucleic Acid HybridizationPhenotypeT-LymphocytesConceptsT 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 analysisInfection