2022
Citrullination of glucokinase is linked to autoimmune diabetes
Yang ML, Horstman S, Gee R, Guyer P, Lam TT, Kanyo J, Perdigoto AL, Speake C, Greenbaum CJ, Callebaut A, Overbergh L, Kibbey RG, Herold KC, James EA, Mamula MJ. Citrullination of glucokinase is linked to autoimmune diabetes. Nature Communications 2022, 13: 1870. PMID: 35388005, PMCID: PMC8986778, DOI: 10.1038/s41467-022-29512-0.Peer-Reviewed Original ResearchConceptsGlucose-stimulated insulin secretionResult of inflammationType 1 diabetesBeta-cell metabolismPancreatic beta cellsAutoimmune diabetesNOD miceAutoreactive CD4Inflammatory cytokinesAutoimmune biomarkersInsulin secretionT cellsBeta cellsType 1InflammationBiologic activityReactive oxygen speciesDiabetesPost-translational modificationsDiabetes biomarkersGlycogen synthesisBiomarkersCitrullinationGlucokinaseOxygen species
2018
Epidermal growth factor receptor peptide vaccination induces cross-reactive immunity to human EGFR, HER2, and HER3
Doyle HA, Koski RA, Bonafé N, Bruck RA, Tagliatela SM, Gee RJ, Mamula MJ. Epidermal growth factor receptor peptide vaccination induces cross-reactive immunity to human EGFR, HER2, and HER3. Cancer Immunology, Immunotherapy 2018, 67: 1559-1569. PMID: 30056598, PMCID: PMC7268894, DOI: 10.1007/s00262-018-2218-9.Peer-Reviewed Original ResearchConceptsAntibody-dependent cell-mediated cytotoxicityEpidermal growth factor receptorAnti-tumor immunityMonoclonal antibody treatmentAntibody treatmentImmune serumElicit anti-tumor immunityAnti-EGFR monoclonal antibodiesHuman epidermal growth factor receptorPeptide-based vaccinationCross-reactive immunityT cell responsesCell-mediated cytotoxicityAnti-tumor antibodiesNatural anti-tumor antibodiesMDA-MB-453Tumor cell killingErbB family membersGrowth factor receptorPeptide vaccinationStandard chemotherapyImmune toleranceCurrent treatmentDrug infusionRadiation therapy
2012
Lupus autoimmunity altered by cellular methylation metabolism
Yang ML, Gee AJ, Gee RJ, Zurita-Lopez CI, Khare S, Clarke SG, Mamula MJ. Lupus autoimmunity altered by cellular methylation metabolism. Autoimmunity 2012, 46: 21-31. PMID: 23039363, PMCID: PMC3543504, DOI: 10.3109/08916934.2012.732133.Peer-Reviewed Original ResearchConceptsS-adenosylmethionineTCR-mediated T cell proliferationImmune responseCell proliferationLupus-prone MRL/lpr miceT-cell activation markersMRL/lpr miceTh1/Th2 cytokinesB cell immune responsesMajor methyl donorDimethylarginine residuesT cell immunityCell activation markersT cell autoreactivityT cell responsesMethylated proteinsCell immune responsesTarget of autoimmunityT cell proliferationIncubation of cellsB cell proliferationDose-dependent mannerSAM metabolismLupus autoimmunityMethylation status
2007
Antigen presentation and transfer between B cells and macrophages
Harvey BP, Gee RJ, Haberman AM, Shlomchik MJ, Mamula MJ. Antigen presentation and transfer between B cells and macrophages. European Journal Of Immunology 2007, 37: 1739-1751. PMID: 17534863, DOI: 10.1002/eji.200636452.Peer-Reviewed Original ResearchConceptsAntigen-presenting cellsB cell receptorCD4 T cellsB cellsT cellsImmune responseOngoing immune responseTransfer of antigenDendritic cellsAntigen transferAntigen presentationMHC compatibilitySelf proteinsSpecific antigenCell receptorAntigenMacrophagesActivation stateImmunityNovel mechanismCellsPrior findingsReceptorsResponseAltered immunogenicity of isoaspartate containing proteins
Doyle HA, Gee RJ, Mamula MJ. Altered immunogenicity of isoaspartate containing proteins. Autoimmunity 2007, 40: 131-137. PMID: 17453712, DOI: 10.1080/08916930601165180.Peer-Reviewed Original ResearchConceptsPost-translational modificationsIsoaspartyl residuesSuch post-translational modificationsContaining ProteinBiological processesLymphocyte developmentIsoaspartic acidCytochrome cProteinAspartic acidCathepsin DCathepsin digestionPigeon cytochrome cResiduesAntigen processingAltered immunogenicityCellsImmune systemNatural modificationBone marrowToleranceD. AdditionallyEnzymeSpontaneous conversionAcid
2006
Intracellular Protein Modification Associated with Altered T Cell Functions in Autoimmunity
Yang ML, Doyle HA, Gee RJ, Lowenson JD, Clarke S, Lawson BR, Aswad DW, Mamula MJ. Intracellular Protein Modification Associated with Altered T Cell Functions in Autoimmunity. The Journal Of Immunology 2006, 177: 4541-4549. PMID: 16982891, DOI: 10.4049/jimmunol.177.7.4541.Peer-Reviewed Original ResearchConceptsAutoimmune miceNZB/W miceAltered T cell functionT-cell proliferative defectsNZB/WMRL/lprT cell functionStrains of miceImmunologic responseW miceAntigenic stimulationT cellsT lymphocytesMRL miceMiceCell functionIntracellular levelsProliferative defectPhysiologic pHAgeNonenzymatic modificationAutoimmunityLymphocytesProtein processingKidneyB Cells Drive Early T Cell Autoimmunity In Vivo prior to Dendritic Cell-Mediated Autoantigen Presentation
Yan J, Harvey BP, Gee RJ, Shlomchik MJ, Mamula MJ. B Cells Drive Early T Cell Autoimmunity In Vivo prior to Dendritic Cell-Mediated Autoantigen Presentation. The Journal Of Immunology 2006, 177: 4481-4487. PMID: 16982884, DOI: 10.4049/jimmunol.177.7.4481.Peer-Reviewed Original ResearchConceptsAutoreactive T cellsDendritic cellsT cellsB cellsAutoantigen-specific B cellsAutoimmune T cell responsesSelf-reactive T cellsAutoantigen-presenting cellsExposure of autoantigensT cell autoimmunityT cell responsesTransgenic mouse modelAutoantigen presentationCell autoimmunityIg transgenic mouse modelProfessional APCsSelf-AgMouse modelEffective APCsCell responsesVivo studiesAutoimmunityLupusAPCCellsIsoaspartyl Post-translational Modification Triggers Anti-tumor T and B Lymphocyte Immunity*
Doyle HA, Zhou J, Wolff MJ, Harvey BP, Roman RM, Gee RJ, Koski RA, Mamula MJ. Isoaspartyl Post-translational Modification Triggers Anti-tumor T and B Lymphocyte Immunity*. Journal Of Biological Chemistry 2006, 281: 32676-32683. PMID: 16950786, DOI: 10.1074/jbc.m604847200.Peer-Reviewed Original ResearchConceptsTRP-2 peptideImmune toleranceT cellsNormal immune tolerancePeptide-pulsed targetsPeptide-immunized miceCytotoxic T lymphocytesB cell toleranceStrong immune responseTetramer analysisLymphocyte immunityMelanoma antigensT lymphocytesImmune responseCell toleranceImmune systemPost-translational protein modificationTyrosinase-related proteinCD8AntigenTumor proteinCellsImmunizationLymphocytesMice
2003
A Failure to Repair Self-Proteins Leads to T Cell Hyperproliferation and Autoantibody Production
Doyle HA, Gee RJ, Mamula MJ. A Failure to Repair Self-Proteins Leads to T Cell Hyperproliferation and Autoantibody Production. The Journal Of Immunology 2003, 171: 2840-2847. PMID: 12960305, DOI: 10.4049/jimmunol.171.6.2840.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutoantibodiesAutoantigensBone Marrow TransplantationCD28 AntigensCell DivisionImmunophenotypingIsoaspartic AcidLupus Erythematosus, SystemicLymph NodesLymphocyte ActivationLymphoid TissueMiceMice, Inbred C57BLMice, KnockoutMitogensPhosphorylationProtein D-Aspartate-L-Isoaspartate MethyltransferaseReceptors, Antigen, T-CellSignal TransductionT-LymphocytesConceptsProtein carboxyl methyltransferasePhosphorylation of membersSpontaneous posttranslational modificationAg receptor stimulationCarboxyl methyltransferasePosttranslational modificationsBiological functionsT cell hyperproliferationCell homeostasisCell stressImmune toleranceT cellsT cell homeostasisSystemic lupus erythematosusPeripheral immune toleranceWild-type miceCell hyperproliferationAnti-DNA autoantibodiesHomeostasisLupus erythematosusAutoantibody productionAutoimmune pathologyKidney pathologyT lymphocytesEffector functions
1999
B7 costimulation in the development of lupus: autoimmunity arises either in the absence of B7.1/B7.2 or in the presence of anti-b7.1/B7.2 blocking antibodies.
Liang B, Gee RJ, Kashgarian MJ, Sharpe AH, Mamula MJ. B7 costimulation in the development of lupus: autoimmunity arises either in the absence of B7.1/B7.2 or in the presence of anti-b7.1/B7.2 blocking antibodies. The Journal Of Immunology 1999, 163: 2322-9. PMID: 10438978, DOI: 10.4049/jimmunol.163.4.2322.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, AntinuclearAntibodies, BlockingAntibodies, MonoclonalAntigens, CDAutoantibodiesB7-1 AntigenB7-2 AntigenDNAGlomerulonephritisKidneyLupus Erythematosus, SystemicLymphocyte ActivationMembrane GlycoproteinsMiceMice, Inbred BALB CMice, Inbred C57BLMice, Inbred MRL lprMice, KnockoutRibonucleoproteins, Small NuclearConceptsMRL-lpr/lpr miceAnti-dsDNA autoantibodiesSystemic lupus erythematosusLpr miceAutoantibody expressionLupus erythematosusB7 costimulationAb treatmentMRL-lpr/lpr murine modelAnti-small nuclear ribonucleoproteinAge-matched wild-type miceHuman systemic lupus erythematosusMurine systemic lupus erythematosusDevelopment of lupusB7 costimulatory signalsWild-type miceB7.1/B7.2Autoantibody titersSevere glomerulonephritisSurface of APCsAutoantibody profileUntreated miceCostimulatory moleculesKidney pathologyT lymphocytesIsoaspartyl Post-translational Modification Triggers Autoimmune Responses to Self-proteins*
Mamula M, Gee R, Elliott J, Sette A, Southwood S, Jones P, Blier P. Isoaspartyl Post-translational Modification Triggers Autoimmune Responses to Self-proteins*. Journal Of Biological Chemistry 1999, 274: 22321-22327. PMID: 10428801, DOI: 10.1074/jbc.274.32.22321.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAspartic AcidAutoantibodiesAutoimmunityB-LymphocytesBinding, CompetitiveCytochrome c GroupHistocompatibility Antigens Class IIImmune ToleranceIsomerismLymphocyte ActivationMiceMice, Inbred MRL lprMolecular Sequence DataNuclear Magnetic Resonance, BiomolecularPeptide FragmentsProtein BindingProtein Processing, Post-TranslationalRibonucleoproteins, Small NuclearT-LymphocytesConceptsSystemic lupus erythematosusAutoimmune responseT cell autoimmune responsesHuman systemic lupus erythematosusInitiation of autoimmunityT cell compartmentT cell responsesImmunization of miceFunctioning immune systemLupus erythematosusSelf antigensAutoimmune diseasesImmunologic stimuliC-peptidePeptide autoantigensImmune systemCell responsesForeign pathogensImmunizationCytochrome c peptideMiceCell compartmentPresent studyPeptidesResponseT cell autoimmunity in Ig transgenic mice.
Shinde S, Gee R, Santulli-Marotto S, Bockenstedt L, Clarke S, Mamula M. T cell autoimmunity in Ig transgenic mice. The Journal Of Immunology 1999, 162: 7519-24. PMID: 10358207, DOI: 10.4049/jimmunol.162.12.7519.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigen PresentationAutoantigensB-LymphocytesCD4-Positive T-LymphocytesFlow CytometryGenes, ImmunoglobulinHistocompatibility Antigens Class IILupus Erythematosus, SystemicMiceMice, Inbred C57BLMice, Inbred MRL lprMice, TransgenicPeptidesReceptors, Antigen, B-CellRibonucleoproteins, Small NuclearT-LymphocytesConceptsAutoreactive T cellsCD4 T cellsT cellsTransgenic miceB lymphocytesMRL-lpr/lpr miceLpr/lpr miceT cell autoimmunityAutoreactive B lymphocytesSystemic lupus erythematosusWild-type C57BL/6Wild-type miceC57BL/6 transgenic miceTransgenic B lymphocytesIg transgenic miceB cell APCCell autoimmunityLupus erythematosusLpr miceT lymphocytesMurine modelImmature phenotypeLymphocytesVivo activationMice
1995
Self-peptides in the initiation of lupus autoimmunity.
Bockenstedt LK, Gee RJ, Mamula MJ. Self-peptides in the initiation of lupus autoimmunity. The Journal Of Immunology 1995, 154: 3516-24. PMID: 7534800, DOI: 10.4049/jimmunol.154.7.3516.Peer-Reviewed Original ResearchConceptsSm small nuclear ribonucleoproteinsT cellsAutoreactive T cell proliferationDiverse autoimmune responseSystemic lupus erythematosusT cell responsesTypes of autoimmunityT cell proliferationD proteinsLupus autoimmunityLupus erythematosusLupus autoantigensAutoimmune responseAb responsesNormal miceForeign AgsSmall nuclear ribonucleoproteinImmune systemCell responsesHigh titersImmunofluorescence patternMolecular mimicsAmino acids 26Mouse lymphocytes