0000000000339555

AUTHOR

Wolfgang Uckert

showing 4 related works from this author

Thymus-derived regulatory T cells are positively selected on natural self-antigen through cognate interactions of high functional avidity

2016

Regulatory T (Treg) cells expressing Foxp3 transcripton factor are essential for immune homeostasis. They arise in the thymus as a separate lineage from conventional CD4+Foxp3- T (Tconv) cells. Here, we show that the thymic development of Treg cells depends on the expression of their endogenous cognate self-antigen. The formation of these cells was impaired in mice lacking this self-antigen, while Tconv cell development was not negatively affected. Thymus-derived Treg cells were selected by self-antigens in a specific manner, while autoreactive Tconv cells were produced through degenerate recognition of distinct antigens. These distinct modes of development were associated with the expressi…

0301 basic medicineCell typeCancer ResearchEncephalomyelitis Autoimmune ExperimentalMultiple Sclerosis[SDV]Life Sciences [q-bio]ImmunologyReceptors Antigen T-CellEndogenyT-Cell Antigen Receptor Specificitychemical and pharmacologic phenomenaThymus GlandBiologymedicine.disease_causeAutoantigensT-Lymphocytes RegulatoryAutoimmunity03 medical and health sciencesMice0302 clinical medicineAntigenT-Lymphocyte SubsetsmedicineImmunology and AllergyAnimalsHumansAvidityCTLA-4 AntigenReceptorClonal Selection Antigen-MediatedCells CulturedMice KnockoutCell growthFOXP3Forkhead Transcription Factorshemic and immune systemsPeptide Fragments[SDV] Life Sciences [q-bio]Mice Inbred C57BL030104 developmental biologyInfectious DiseasesImmunologyMyelin-Oligodendrocyte Glycoprotein030215 immunology
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T cells engineered to express a T-cell receptor specific for glypican-3 to recognize and kill hepatoma cells in vitro and in mice

2015

Background & Aims Cancer therapies are being developed based on our ability to direct T cells against tumor antigens. Glypican-3 (GPC3) is expressed by 75% of all hepatocellular carcinomas (HCC), but not in healthy liver tissue or other organs. We aimed to generate T cells with GPC3-specific receptors that recognize HCC and used them to eliminate GPC3-expressing xenograft tumors grown from human HCC cells in mice. Methods We used mass spectrometry to obtain a comprehensive peptidome from GPC3-expressing hepatoma cells after immune-affinity purification of human leukocyte antigen (HLA)-A2 and bioinformatics to identify immunodominant peptides. To circumvent GPC3 tolerance resulting from feta…

Cytotoxicity ImmunologicCancer Immunotherapy ; Immune Response ; Liver Cancer ; Tumor-associated AntigensCarcinoma HepatocellularTime FactorsCell SurvivalMice SCIDCD8-Positive T-LymphocytesBiologyLymphocyte ActivationTransfectionImmunotherapy AdoptiveInterferon-gammaInterleukin 21GlypicansHLA-A2 AntigenAnimalsHumansCytotoxic T cellIL-2 receptorAntigen-presenting cellInterleukin 3HepatologyImmunodominant EpitopesZAP70Liver NeoplasmsGastroenterologyDendritic CellsHep G2 CellsNatural killer T cellXenograft Model Antitumor AssaysMolecular biologyCoculture TechniquesGenes T-Cell ReceptorInterleukin 12FemaleGenetic Engineering
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TCR-Ligand koff rate correlates with the protective capacity of antigen-specific CD8+ T cells for adoptive transfer.

2013

Adoptive immunotherapy is a promising therapeutic approach for the treatment of chronic infections and cancer. Thereby, T cells within a certain range of high avidity for their cognate ligand are believed to be most effective. T cell receptor (TCR) transfer experiments indicate that a major part of avidity is hard-wired within the structure of the TCR. Unfortunately, rapid measurement of structural avidity of TCRs is difficult on living T cells. We developed a technology, where dissociation (koff-rate) of truly monomeric peptide major histocompatibility complex (pMHC) molecules bound to surface expressed TCRs can be monitored by real-time microscopy in a highly reliable manner. A first eval…

MaleAdoptive cell transferT cellmedicine.medical_treatmentReceptors Antigen T-CellGenes MHC Class Ichemical and pharmacologic phenomenaStreptamerBiologyCD8-Positive T-LymphocytesMajor histocompatibility complexImmunotherapy AdoptiveArticleMicemedicineCytotoxic T cellAnimalsHumansAvidityCells CulturedT-cell receptorGeneral MedicineImmunotherapyAdoptive Transfermedicine.anatomical_structureImmunologybiology.proteinFemale
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T cells expressing a chimeric antigen receptor that binds hepatitis B virus envelope proteins control virus replication in mice.

2013

Background & Aims Antiviral agents suppress hepatitis B virus (HBV) replication but do not clear the infection. A strong effector T-cell response is required to eradicate HBV, but this does not occur in patients with chronic infection. T cells might be directed toward virus-infected cells by expressing HBV-specific receptors and thereby clear HBV and help to prevent development of liver cancer. In mice, we studied whether redirected T cells can engraft after adoptive transfer, without prior T-cell depletion, and whether the large amounts of circulating viral antigens inactivate the transferred T cells or lead to uncontrolled immune-mediated damage. Methods CD8 + T cells were isolated from m…

Adoptive cell transferHepatitis B virusRecombinant Fusion ProteinsReceptors Antigen T-CellMice TransgenicAdoptive T-Cell TherapyCD8-Positive T-Lymphocytesmedicine.disease_causeVirus ReplicationInterleukin 21MiceViral Envelope ProteinsmedicineCytotoxic T cellAnimalsHumansIL-2 receptorAntigen-presenting cellHepatitis B virusCD40HepatologybiologyZAP70Gastroenterologyvirus diseasesHepatocellular CarcinomaVirologyMolecular biologyAdoptive TransferMice Inbred C57BLLiverbiology.proteinImmunotherapyChronic Hepatitis BGastroenterology
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