2023
ScRNA-seq defines dynamic T-cell subsets in longitudinal colon and peripheral blood samples in immune checkpoint inhibitor-induced colitis
Mann J, Lucca L, Austin M, Merkin R, Robert M, Al Bawardy B, Raddassi K, Aizenbud L, Joshi N, Hafler D, Abraham C, Herold K, Kluger H. ScRNA-seq defines dynamic T-cell subsets in longitudinal colon and peripheral blood samples in immune checkpoint inhibitor-induced colitis. Journal For ImmunoTherapy Of Cancer 2023, 11: e007358. PMID: 37586769, PMCID: PMC10432652, DOI: 10.1136/jitc-2023-007358.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsT cell subsetsCheckpoint inhibitorsImmune environmentImmune checkpoint inhibitor-induced colitisCheckpoint inhibitor-induced colitisPeripheral immune environmentsStages of colitisTreatment of colitisMerkel cell carcinomaT cell populationsPeripheral blood samplesCourse of progressionT cell receptorMultiple tumor typesAlternative cancer therapyCommon toxicitiesICI colitisTreatment discontinuationAdverse eventsBiologic therapyImmune suppressionCell carcinomaColitisBlood samples
2022
TCR-sequencing in cancer and autoimmunity: barcodes and beyond
Pauken KE, Lagattuta KA, Lu BY, Lucca LE, Daud AI, Hafler DA, Kluger HM, Raychaudhuri S, Sharpe AH. TCR-sequencing in cancer and autoimmunity: barcodes and beyond. Trends In Immunology 2022, 43: 180-194. PMID: 35090787, PMCID: PMC8882139, DOI: 10.1016/j.it.2022.01.002.Peer-Reviewed Original ResearchConceptsT cell receptorT cellsMolecular barcodesProgrammed Death-1 BlockadeTCR sequencesDeath-1 blockadeUnique TCR sequencesNaïve T cellsT cell functionCell divisionMolecular phenotypesBarcodesImmune responseAntigen specificitySingle cellsCell receptorCell functionRecent technological advancesCancerTCR dataCells
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 clones
2003
Rapamycin-resistant Proliferation of CD8+ T Cells Correlates with p27 kip1 Down-regulation and bcl-xL Induction, and Is Prevented by an Inhibitor of Phosphoinositide 3-Kinase Activity*
Slavik JM, Lim DG, Burakoff SJ, Hafler DA. Rapamycin-resistant Proliferation of CD8+ T Cells Correlates with p27 kip1 Down-regulation and bcl-xL Induction, and Is Prevented by an Inhibitor of Phosphoinositide 3-Kinase Activity*. Journal Of Biological Chemistry 2003, 279: 910-919. PMID: 14573608, DOI: 10.1074/jbc.m209733200.Peer-Reviewed Original ResearchMeSH KeywordsAnnexin A5Antibiotics, AntineoplasticBcl-X ProteinCD28 AntigensCD3 ComplexCD8-Positive T-LymphocytesCell Cycle ProteinsCell DivisionColoring AgentsCyclin DCyclin-Dependent Kinase Inhibitor p27CyclinsDose-Response Relationship, DrugDown-RegulationEnzyme InhibitorsEstersFluoresceinsHumansKineticsLymphocytesPhosphatidylinositol 3-KinasesProtein BindingProto-Oncogene Proteins c-bcl-2Signal TransductionSirolimusT-LymphocytesTime FactorsTumor Suppressor ProteinsConceptsInhibitor of phosphoinositideT cell receptorMammalian cell typesCell receptorBcl-xL inductionAction of rapamycinBcl-xL expressionT cellsHuman cellsCell survivalP27 Kip1Resistant proliferationCell typesPhosphoinositideHuman CD8RapamycinCellular proliferationEffect of rapamycinMicrobial infectionsCell populationsHigh-affinity T-cell receptorsSelective immunosuppressive effectT Cells CorrelateT cell populationsProliferationAllelic Variation of MHC Structure Alters Peptide Ligands to Induce Atypical Partial Agonistic CD8+ T Cell Function
Lim DG, Slavik JM, Bourcier K, Smith KJ, Hafler DA. Allelic Variation of MHC Structure Alters Peptide Ligands to Induce Atypical Partial Agonistic CD8+ T Cell Function. Journal Of Experimental Medicine 2003, 198: 99-109. PMID: 12847139, PMCID: PMC2196091, DOI: 10.1084/jem.20021796.Peer-Reviewed Original ResearchConceptsT cell functionT cell clonesCell functionReactive T cell clonesCell clonesT cell responsesDifferent T cell responsesIndividual T cell clonesHLA-A2 moleculesAltered peptide ligandHLA-A2 peptideRecognition of MHCT cell receptorMHC-peptide complexesPolymorphic amino acidsFunctional outcomeHLA-A2Peptide ligandsAgonist functionMHC moleculesCell responsesEarly intracellularLong-term expressionCell receptorAntigen recognition
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 virusDecreases 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
A novel population of B7‐1+ T cells producing intracellular IL‐4 is decreased in patients with multiple sclerosis
Kipp B, Bar‐Or A, Gausling R, Oliveira E, Fruhan S, Stuart W, Hafler D. A novel population of B7‐1+ T cells producing intracellular IL‐4 is decreased in patients with multiple sclerosis. European Journal Of Immunology 2000, 30: 2092-2100. PMID: 10940899, DOI: 10.1002/1521-4141(200007)30:7<2092::aid-immu2092>3.0.co;2-7.Peer-Reviewed Original ResearchConceptsT cell receptorIntracellular IL-4Multiple sclerosisT cellsB7-1IL-4Autoimmune diseasesTNF-alphaIFN-gammaIL-4-producing T cellsLittle IL-4Immunoregulatory T cellsIL-4 productionIntracellular IFN-gammaT cell populationsLittle IFN-gammaNovel populationDiverse TCR repertoireMHC class IIHuman T cellsShort-term cultureCell surface moleculesTCR repertoireNormal subjectsPatientsGlatiramer acetate (Copaxone®) induces degenerate, Th2-polarized immune responses in patients with multiple sclerosis
Duda PW, Schmied MC, Cook SL, Krieger JI, Hafler DA. Glatiramer acetate (Copaxone®) induces degenerate, Th2-polarized immune responses in patients with multiple sclerosis. Journal Of Clinical Investigation 2000, 105: 967-976. PMID: 10749576, PMCID: PMC377485, DOI: 10.1172/jci8970.Peer-Reviewed Original ResearchMeSH KeywordsAdultAmino Acid SequenceCell DivisionCells, CulturedCross ReactionsEpitopes, T-LymphocyteFemaleGlatiramer AcetateHumansImmunodominant EpitopesImmunosuppressive AgentsInterferon-gammaInterleukin-5Leukocytes, MononuclearLigandsMaleMiddle AgedMolecular Sequence DataMultiple SclerosisMyelin Basic ProteinMyelin SheathPeptide FragmentsPeptidesTetanus ToxoidTh2 CellsConceptsT cell responsesMultiple sclerosisGlatiramer acetateT cellsAntigen-specific T cell responsesTh2-polarized immune responseCross-reactive T cellsAlters immune functionHuman autoimmune diseasesAcetate inducesCross-reactive responsesT cell receptorT cell linesImmune deviationMost patientsTh2 typeAutoimmune disordersTh2 cytokinesAutoimmune diseasesDaily injectionsIL-13IL-5Th2 cellsHealthy subjectsImmune responseParadoxical inhibition of T-cell function in response to CTLA-4 blockade; heterogeneity within the human T-cell population
Anderson D, Bieganowska K, Bar-Or A, Oliveira E, Carreno B, Collins M, Hafler D. Paradoxical inhibition of T-cell function in response to CTLA-4 blockade; heterogeneity within the human T-cell population. Nature Medicine 2000, 6: 211-214. PMID: 10655112, DOI: 10.1038/72323.Peer-Reviewed Original ResearchConceptsCTLA-4 blockadeT cell populationsCTLA-4T cellsMonoclonal antibodiesB7-1B7-2Immune responseCytotoxic T-lymphocyte antigen-4Whole T cell populationsT-lymphocyte antigen-4Antigen-specific T cellsT cell activation stateHuman T cell populationsT cell functionT cell receptor signalsCo-stimulatory signalsDifferent T cellsT cell stimulationEffect of B7T cell activationActivation stateT cell receptorHuman T cellsFab fragments
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 transcriptsCellsJalpha18Valpha24
1998
Natural killer activating receptors trigger interferon γ secretion from T cells and natural killer cells
Mandelboim O, Kent S, Davis D, Wilson S, Okazaki T, Jackson R, Hafler D, Strominger J. Natural killer activating receptors trigger interferon γ secretion from T cells and natural killer cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 1998, 95: 3798-3803. PMID: 9520447, PMCID: PMC19917, DOI: 10.1073/pnas.95.7.3798.Peer-Reviewed Original ResearchConceptsNatural killer cell activating receptorsT cellsNK cellsInterferon γ secretionSubset of CD8Target cellsHuman class I major histocompatibility complex (MHC) moleculesNatural killer cellsInterferon-gamma secretionGammadelta T cellsMajor histocompatibility complex moleculesAlphabeta T cellsClass I MHC moleculesClass I major histocompatibility complex moleculesTypes of lymphocytesMHC class IHistocompatibility complex moleculesI MHC moleculesT cell receptorEnhancement of proliferationΓ secretionGamma secretionNatural killerKiller cellsActivating receptors
1997
Constitutive expression of costimulatory molecules by human microglia and its relevance to CNS autoimmunity
Dangond F, Windhagen A, Groves C, Hafler D. Constitutive expression of costimulatory molecules by human microglia and its relevance to CNS autoimmunity. Journal Of Neuroimmunology 1997, 76: 132-138. PMID: 9184642, DOI: 10.1016/s0165-5728(97)00043-x.Peer-Reviewed Original ResearchConceptsCentral nervous systemCostimulatory moleculesHuman microgliaMyelin-reactive T cellsTh1 T cell responsesExpression of B7.1Reactive T cellsT cell responsesMultiple sclerosis plaquesT cell surface moleculesB7.2 costimulatory moleculesMHC-antigen complexesT cell activationT cell receptorCNS autoimmunityCNS inflammationB7.2 expressionBiopsy specimensB7 familyT cellsNormal brainMicrogliaNervous systemB7.1High expressionDirect 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
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 substitutionsCytotoxic γδ T Lymphocytes Associated with an Epstein–Barr Virus-Induced Posttransplantation Lymphoproliferative Disorder
Rothenberg M, Weber W, Longtine J, Hafler D. Cytotoxic γδ T Lymphocytes Associated with an Epstein–Barr Virus-Induced Posttransplantation Lymphoproliferative Disorder. Clinical Immunology 1996, 80: 266-272. PMID: 8811046, DOI: 10.1006/clin.1996.0122.Peer-Reviewed Original ResearchConceptsGamma delta T cellsDelta T cellsGamma delta T-cell receptorDelta T-cell receptorPosttransplantation lymphoproliferative diseaseT cellsBrain lesionsT cell receptorLymphoproliferative diseaseCell receptorInflammatory brain lesionsPosttransplantation lymphoproliferative disorderEpstein-Barr virusCultured T cell linesCentral nervous systemT cell linesHuman brain tissueLymphoproliferative disordersAutoimmune diseasesInflammatory processVirus immunityNervous systemBrain tissueLesionsTarget cells
1995
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
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
Structural requirements for binding of an immunodominant myelin basic protein peptide to DR2 isotypes and for its recognition by human T cell clones.
Wucherpfennig KW, Sette A, Southwood S, Oseroff C, Matsui M, Strominger JL, Hafler DA. Structural requirements for binding of an immunodominant myelin basic protein peptide to DR2 isotypes and for its recognition by human T cell clones. Journal Of Experimental Medicine 1994, 179: 279-290. PMID: 7505801, PMCID: PMC2191316, DOI: 10.1084/jem.179.1.279.Peer-Reviewed Original ResearchConceptsT cell clonesMyelin basic proteinMultiple sclerosisCell clonesT cellsImmunodominant myelin basic protein peptideMBP-reactive T cellsMajor histocompatibility complex class IIDR2 haplotypeHistocompatibility complex class IIImmunodominant T cell epitopesHuman T cell clonesAutoreactive T cellsReactive T cellsT cell epitopesMyelin basic protein peptideT cell stimulationT cell receptorMS patientsDRB1 moleculesDR2 antigenRestriction elementsCell epitopesTarget antigenClass II
1993
Increased Protein Kinase C Activity in Human Memory T Cells
Höllsberg P, Melinek J, Benjamin D, Hafler D. Increased Protein Kinase C Activity in Human Memory T Cells. Cellular Immunology 1993, 149: 170-179. PMID: 8099849, DOI: 10.1006/cimm.1993.1145.Peer-Reviewed Original ResearchConceptsCD26 T cellsMemory T cellsT cell populationsMemory T cell populationsT cellsT cell receptorProliferative responseCell populationsPeripheral blood T cellsHuman memory T cellsMemory T cell functionCD26 antigen expressionT-cell surface antigensPKC activityBlood T cellsT cell functionTCR/CD3 pathwayDifferentiated T cellsCell surface antigensCD26 mAbCD26- subsetAntigen challengeAntigen expressionCD26 antigenCD26 expression
1992
Early signaling defects in human T cells anergized by T cell presentation of autoantigen.
LaSalle JM, Tolentino PJ, Freeman GJ, Nadler LM, Hafler DA. Early signaling defects in human T cells anergized by T cell presentation of autoantigen. Journal Of Experimental Medicine 1992, 176: 177-186. PMID: 1535366, PMCID: PMC2119294, DOI: 10.1084/jem.176.1.177.Peer-Reviewed Original ResearchConceptsAntigen-presenting cellsT cell presentationPhorbol myristate acetateT cellsAnergized T cellsCell presentationL cell transfectantsProliferative responseAlpha CD3B cellsMajor histocompatibility complex classHuman T cell clonesPrimary proliferative responsesAllogeneic B cellsT cell anergyT cell clonesHistocompatibility complex classInduction of anergyInterferon-gamma mRNANormal proliferative responseT cell activationCD2 monoclonal antibodiesT cell receptorCell transfectantsPresence of costimulation