2022
A discovery-based proteomics approach identifies protein disulphide isomerase (PDIA1) as a biomarker of β cell stress in type 1 diabetes
Syed F, Singhal D, Raedschelders K, Krishnan P, Bone R, McLaughlin M, Van Eyk J, Mirmira R, Yang M, Mamula M, Wu H, Liu X, Evans-Molina C. A discovery-based proteomics approach identifies protein disulphide isomerase (PDIA1) as a biomarker of β cell stress in type 1 diabetes. EBioMedicine 2022, 87: 104379. PMID: 36463755, PMCID: PMC9719098, DOI: 10.1016/j.ebiom.2022.104379.Peer-Reviewed Original ResearchConceptsT-cell adoptive transferCell adoptive transferNOD miceNOD-SCID miceType 1 diabetesΒ-cell stressAdoptive transferPre-diabetic NOD miceFemale NOD miceNon-diabetic controlsRecent-onset T1DSerum of childrenDistinct mouse modelsΒ-cell functionHuman organ donorsWeeks of agePotential human biomarkersDisease-related changesΒ-cell deathCell protein expressionNOD isletsAutoantibody positivityDiabetes onsetT1D developmentImmune activation
2008
Sequential autoantigenic determinants of the small nuclear ribonucleoprotein Sm D shared by human lupus autoantibodies and MRL Ipr/lpr antibodies
JAMES J, MAMULA M, HARLEY J. Sequential autoantigenic determinants of the small nuclear ribonucleoprotein Sm D shared by human lupus autoantibodies and MRL Ipr/lpr antibodies. Clinical & Experimental Immunology 2008, 98: 419-426. PMID: 7527740, PMCID: PMC1534503, DOI: 10.1111/j.1365-2249.1994.tb05507.x.Peer-Reviewed Original ResearchConceptsMRL-lpr/lpr miceLpr/lpr miceAutoimmune serologySLE patientsLpr micePatient seraEpitope 5Systemic lupus erythematosus (SLE) patient seraEpstein-Barr nuclear antigen 1Lupus patients' seraNuclear antigen 1Precipitin-positive seraHuman lupus autoantibodiesNormal human serumMajor antigenic regionSm DPositive patientsAutoimmune responseSm autoantigenLupus autoantibodiesNormal controlsPatientsEpitope 4Mouse serumAntigen 1
2001
From T to B and back again: positive feedback in systemic autoimmune disease
Shlomchik M, Craft J, Mamula M. From T to B and back again: positive feedback in systemic autoimmune disease. Nature Reviews Immunology 2001, 1: 147-153. PMID: 11905822, DOI: 10.1038/35100573.Peer-Reviewed Original ResearchConceptsSystemic autoimmune diseaseAutoimmune diseasesPrototypical systemic autoimmune diseaseSystemic lupus erythematosusPerpetuation of autoimmunityLoss of toleranceAutoantigen targetsLupus erythematosusAutoimmune stateB cellsImmune systemNuclear autoantigensDiseaseErythematosusAutoimmunityAutoantigensStructural Integrity of Histone H2B in Vivo Requires the Activity of Protein l-IsoaspartateO-Methyltransferase, a Putative Protein Repair Enzyme*
Young A, Carter W, Doyle H, Mamula M, Aswad D. Structural Integrity of Histone H2B in Vivo Requires the Activity of Protein l-IsoaspartateO-Methyltransferase, a Putative Protein Repair Enzyme*. Journal Of Biological Chemistry 2001, 276: 37161-37165. PMID: 11479322, DOI: 10.1074/jbc.m106682200.Peer-Reviewed Original ResearchConceptsHistone H2BIsoaspartate (D-aspartate) O-methyltransferaseNormal gene regulationProtein repair enzymePIMT knockout miceActivity of proteinsRat PC12 cellsGene regulationProtein functionHistone H2B.Core histonesNuclear proteinsSubcellular fractionationProtein agingRepair enzymesH2BO-methyltransferaseAdenosine dialdehydeMethyltransferase inhibitorProtein LHistonesAsp-XaaPC12 cellsIsoAspStoichiometric levelsLupus autoantigens: Their origins, forms, and presentation
Doyle H, Yan J, Liang B, Mamula M. Lupus autoantigens: Their origins, forms, and presentation. Immunologic Research 2001, 24: 131-147. PMID: 11594452, DOI: 10.1385/ir:24:2:131.Peer-Reviewed Original ResearchConceptsSystemic lupus erythematosusMaintenance of autoimmunityT cell compartmentCentral lymphoid organsT cell developmentAutoimmune processLupus erythematosusAntigenic sinAutoreactive cellsAutoimmune diseasesLymphoid organsPresenting cellsB lymphocytesImmune systemAutoimmunityCell compartmentNumber of mechanismsCell developmentInductionErythematosusCellsLupusForeign proteinsLymphocytesCostimulation
2000
Autoantibody Responses and Pathology Regulated by B7-1 and B7-2 Costimulation in MRL/lpr Lupus
Liang B, Kashgarian M, Sharpe A, Mamula M. Autoantibody Responses and Pathology Regulated by B7-1 and B7-2 Costimulation in MRL/lpr Lupus. The Journal Of Immunology 2000, 165: 3436-3443. PMID: 10975864, DOI: 10.4049/jimmunol.165.6.3436.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, AntinuclearAntigens, CDAntigens, Differentiation, B-LymphocyteAutoantibodiesB7-1 AntigenB7-2 AntigenBiomarkersComplement C3DNAImmunoglobulin GImmunoglobulin IsotypesImmunoglobulin MKidneyLupus NephritisLymphocyte ActivationMembrane GlycoproteinsMiceMice, Inbred BALB CMice, Inbred MRL lprMice, KnockoutRibonucleoproteins, Small NuclearT-LymphocytesConceptsMRL-lpr/lpr miceSystemic lupus erythematosusLpr miceB7-2 costimulationB7-1Autoantibody responseB7-2Murine modelCostimulatory signalsAnti-small nuclear ribonucleoproteinMRL/lpr lupusHuman systemic lupus erythematosusB7-1/B7C3 complement depositionAnti-DNA titersAnti-DNA autoantibodiesWild-type animalsImmunotherapeutic interventionsMemory CD4Lupus erythematosusAutoimmune diseasesAutoimmune pathologyC3 depositsComplement depositionT lymphocytes
1999
Isoaspartyl 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 AcidAutoantibodiesAutoimmunityBinding, CompetitiveB-LymphocytesCytochrome 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 studyPeptidesResponse
1998
Autoreactive B Cell Regulation: Peripheral Induction of Developmental Arrest by Lupus-Associated Autoantigens
Santulli-Marotto S, Retter M, Gee R, Mamula M, Clarke S. Autoreactive B Cell Regulation: Peripheral Induction of Developmental Arrest by Lupus-Associated Autoantigens. Immunity 1998, 8: 209-219. PMID: 9492002, DOI: 10.1016/s1074-7613(00)80473-2.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutoantigensB-LymphocytesBone MarrowCell DifferentiationDNA, Single-StrandedEnzyme-Linked Immunosorbent AssayFluorescent Antibody TechniqueGene Rearrangement, B-Lymphocyte, Heavy ChainHematopoietic Stem CellsHybridomasImmune ToleranceLupus Erythematosus, SystemicLymphocyte ActivationMiceMice, Inbred MRL lprMice, TransgenicRibonucleoproteins, Small NuclearSnRNP Core ProteinsSpleenConceptsB cellsAnti-Sm B cellsAnti-ssDNA antibodiesB-cell phenotypeImmature B-cell phenotypeImmature B cellsAutoreactive cellsMurine lupusPeripheral inductionTolerance inductionVH-D-JH rearrangementsTransgenic miceAnti-Sm hybridomasSplenic repertoireCell phenotypeSpontaneous activationCellsInductionLupusImmunizationAutoantigensLater stagesDevelopmental arrestMiceSecretion
1997
Trafficking of Adoptively Transferred B Lymphocytes in B-Lymphocyte-Deficient Mice
Roth R, Mamula M. Trafficking of Adoptively Transferred B Lymphocytes in B-Lymphocyte-Deficient Mice. Journal Of Experimental Biology 1997, 200: 2057-2062. PMID: 9246787, DOI: 10.1242/jeb.200.14.2057.Peer-Reviewed Original ResearchConceptsB cell transferB cellsLymphoid organsB lymphocyte-deficient miceB cell-deficient miceAdoptive transfer studiesB cell distributionNaive B cellsTrafficking patternsAxillary lymphLymph nodesMicroMT micePopliteal lymphRecipient miceSubcutaneous transferIntravenous injectionPeritoneal cavityB lymphocytesInjection siteTransient decreaseCell transferFlow cytometryLymphMicePotential cellular interactionsB Lymphocytes as Autoantigen‐presenting Cells in the Amplification of Autoimmunitya
ROTH R, GEE R, MAMULA M. B Lymphocytes as Autoantigen‐presenting Cells in the Amplification of Autoimmunitya. Annals Of The New York Academy Of Sciences 1997, 815: 88-100. PMID: 9186642, DOI: 10.1111/j.1749-6632.1997.tb52047.x.Peer-Reviewed Original ResearchConceptsB cell-deficient miceCell-deficient miceNaive T cellsT cellsSelf antigensIL-4IL-5B cellsB7-2 costimulatory moleculesAutoantigen-presenting cellsAutoreactive T cellsT cell toleranceAntigen-presenting cellsCytokine mRNA responsesB cell subsetsNaive lymphAutoimmune responseCell subsetsCostimulatory moleculesAntigen presentationCytokine mRNAIFN-gammaB lymphocytesCell toleranceMRNA response
1996
B7 costimulation and autoantigen specificity enable B cells to activate autoreactive T cells.
Roth R, Nakamura T, Mamula M. B7 costimulation and autoantigen specificity enable B cells to activate autoreactive T cells. The Journal Of Immunology 1996, 157: 2924-31. PMID: 8816398, DOI: 10.4049/jimmunol.157.7.2924.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsAntibodies, MonoclonalAntigen PresentationAntigens, CDAutoantigensAutoimmunityB7-1 AntigenB7-2 AntigenBase SequenceB-LymphocytesCell MovementCytochrome c GroupCytokinesFemaleGene Expression RegulationImmunizationLymph NodesLymphocyte ActivationMembrane GlycoproteinsMiceMolecular Sequence DataPeptide FragmentsPolymerase Chain ReactionRatsRNA, MessengerSelf ToleranceSignal TransductionT-Lymphocyte SubsetsConceptsAutoreactive T cellsT cell responsesT cellsB cellsIL-4IL-5Self-AgImmunized B-cell-deficient miceCell responsesAutoimmune T cell responsesB cell-deficient miceB7-1 costimulatory moleculeT cell autoimmunityCell-deficient miceTreatment of miceT cell toleranceNaive T cellsCytokine mRNA responsesCell autoimmunityB7 costimulationCostimulatory moleculesAutoantigen specificityB7-2Cytokine mRNAIFN-gamma
1993
Do B cells drive the diversification of immune responses?
Mamula M, Janeway C. Do B cells drive the diversification of immune responses? Trends In Immunology 1993, 14: 151-152. PMID: 8098941, DOI: 10.1016/0167-5699(93)90274-o.Peer-Reviewed Original ResearchThe inability to process a self-peptide allows autoreactive T cells to escape tolerance.
Mamula M. The inability to process a self-peptide allows autoreactive T cells to escape tolerance. Journal Of Experimental Medicine 1993, 177: 567-571. PMID: 8381158, PMCID: PMC2190887, DOI: 10.1084/jem.177.2.567.Peer-Reviewed Original Research
1992
Breaking T cell tolerance with foreign and self co-immunogens. A study of autoimmune B and T cell epitopes of cytochrome c.
Mamula M, Lin R, Janeway C, Hardin J. Breaking T cell tolerance with foreign and self co-immunogens. A study of autoimmune B and T cell epitopes of cytochrome c. The Journal Of Immunology 1992, 149: 789-95. PMID: 1321851, DOI: 10.4049/jimmunol.149.3.789.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAutoantigensAutoimmunityB-LymphocytesCross ReactionsCytochrome c GroupGene Rearrangement, beta-Chain T-Cell Antigen ReceptorHumansImmune ToleranceLymphocyte ActivationMiceMice, Inbred StrainsRatsReceptors, Antigen, T-Cell, alpha-betaSequence AlignmentSpecies SpecificityT-LymphocytesConceptsT cell responsesT cell toleranceB cellsCell responsesCell toleranceSelf-AgAutoimmune T cell responsesAutoreactive T cell responsesAutoreactive T cell clonesTCR genesAutoimmune B cellsCellular immune responsesImmune B cellsAutoreactive B cellsT cell clonesT cell epitopesAmino acids 54Autoimmune diseasesT cellsImmune responseCell epitopesForeign pathogensModel autoantigenImmunizationCell clones
1991
Induction of autoreactive B cells allows priming of autoreactive T cells.
Lin R, Mamula M, Hardin J, Janeway C. Induction of autoreactive B cells allows priming of autoreactive T cells. Journal Of Experimental Medicine 1991, 173: 1433-1439. PMID: 1851798, PMCID: PMC2190847, DOI: 10.1084/jem.173.6.1433.Peer-Reviewed Original Research
1983
Role of macrophage lipids in regulating tumoricidal activity
Schlager S, Madden L, Meltzer M, Bara S, Mamula M. Role of macrophage lipids in regulating tumoricidal activity. Cellular Immunology 1983, 77: 52-68. PMID: 6301697, DOI: 10.1016/0008-8749(83)90006-0.Peer-Reviewed Original ResearchConceptsM phiTumoricidal activityCellular lipidsTumor cellsTumor cytotoxicityPhagocytic activitySuperoxide releaseTransient increaseMaximal tumoricidal activityPeritoneal M phiFatty acid contentP815 tumor cellsEarly transient increaseRole of cholesterolChol enrichmentTumor target bindingProtein synthesizingProtein synthesisMacrophage lipidsInflammatory functionsCell binding capacityCellular contentControl supernatantsP815 cellsEndogenous levels