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 ComplexAutoantigensBlood DonorsB-LymphocytesCase-Control StudiesCD4-Positive T-LymphocytesCell Line, TransformedHistocompatibility Antigens Class IIHLA-DR AntigensHumansModels, BiologicalPeptidesProteomeSpectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationTandem Mass SpectrometryT-LymphocytesConceptsHLA-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
2010
CIITA 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 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
Polyspecificity of T cell and B cell receptor recognition
Wucherpfennig KW, Allen PM, Celada F, Cohen IR, De Boer R, Garcia KC, Goldstein B, Greenspan R, Hafler D, Hodgkin P, Huseby ES, Krakauer DC, Nemazee D, Perelson AS, Pinilla C, Strong RK, Sercarz EE. Polyspecificity of T cell and B cell receptor recognition. Seminars In Immunology 2007, 19: 216-224. PMID: 17398114, PMCID: PMC2034306, DOI: 10.1016/j.smim.2007.02.012.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigen PresentationB-LymphocytesCD8-Positive T-LymphocytesHumansLigandsLymphocyte ActivationMicePeptidesReceptors, Antigen, T-CellT-Lymphocytes
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
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
2003
In vitro evidence that subcutaneous administration of glatiramer acetate induces hyporesponsive T cells in patients with multiple sclerosis
Schmied M, Duda PW, Krieger JI, Trollmo C, Hafler DA. In vitro evidence that subcutaneous administration of glatiramer acetate induces hyporesponsive T cells in patients with multiple sclerosis. Clinical Immunology 2003, 106: 163-174. PMID: 12706402, DOI: 10.1016/s1521-6616(03)00020-2.Peer-Reviewed Original ResearchConceptsGA-reactive T cellsT cell reactivityT cellsRR-MSMultiple sclerosisCell reactivityT cell peripheral toleranceTh2-type T cellsT cell frequenciesMonths of treatmentT cell hyporesponsivenessT cell populationsT cell nonresponsivenessT cell anergyHyporesponsive T cellsMechanism of actionMyelin antigensGlatiramer acetatePeripheral toleranceCell hyporesponsivenessPeripheral bloodClonal eliminationIL-2Cell anergySubcutaneous administration
2001
Immunological Memory: Contribution of Memory B Cells Expressing Costimulatory Molecules in the Resting State
Bar-Or A, Oliveira E, Anderson D, Krieger J, Duddy M, O’Connor K, Hafler D. Immunological Memory: Contribution of Memory B Cells Expressing Costimulatory Molecules in the Resting State. The Journal Of Immunology 2001, 167: 5669-5677. PMID: 11698439, DOI: 10.4049/jimmunol.167.10.5669.Peer-Reviewed Original ResearchConceptsMemory B cellsB cell subsetsB cellsCell subsetsCostimulatory moleculesB cell memory compartmentMemory responsesImmune memory responseDistinct B cell subsetsHuman memory B cellsHumoral memory responsesHuman B cellsTh cellsImmunological memoryT cellsMemory compartmentPoor APCsMurine systemNovel subpopulationRelative paucityCells
1999
The distinction blurs between an autoimmune versus microbial hypothesis in multiple sclerosis
Hafler DA. The distinction blurs between an autoimmune versus microbial hypothesis in multiple sclerosis. Journal Of Clinical Investigation 1999, 104: 527-529. PMID: 10487765, PMCID: PMC483283, DOI: 10.1172/jci8193.Peer-Reviewed Original ResearchAnimalsAntigen PresentationAntigens, ViralAutoantigensAutoimmune DiseasesCardiovirus InfectionsCross ReactionsDemyelinating DiseasesDisease Models, AnimalDisease ProgressionEncephalomyelitis, Autoimmune, ExperimentalEpitopesHuman T-lymphotropic virus 1HumansMiceMicrogliaModels, ImmunologicalMolecular MimicryMultiple SclerosisMyelin ProteinsParaparesis, Tropical SpasticTheilovirusT-Lymphocyte SubsetsVirus Diseases
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
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 Research
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