A5078470091- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- RNA Interference and Gene Delivery
- Diabetes and associated disorders
- Drug Transport and Resistance Mechanisms
- RNA modifications and cancer
- Force Microscopy Techniques and Applications
- Immune Response and Inflammation
- Cellular Mechanics and Interactions
- Galectins and Cancer Biology
- Single-cell and spatial transcriptomics
- Nanofabrication and Lithography Techniques
- Viral-associated cancers and disorders
- Peripheral Neuropathies and Disorders
- Gene expression and cancer classification
- Glycosylation and Glycoproteins Research
- Inflammasome and immune disorders
- Adenosine and Purinergic Signaling
- Phagocytosis and Immune Regulation
- Advanced Fluorescence Microscopy Techniques
- Amino Acid Enzymes and Metabolism
- Monoclonal and Polyclonal Antibodies Research
- Extracellular vesicles in disease
Ludwig-Maximilians-Universität München
2007-2024
Brigham and Women's Hospital
2005-2007
Harvard University
2005-2007
Joslin Diabetes Center
2005-2007
Inserm
2001
Centre National de la Recherche Scientifique
2001
University of Tübingen
1997-2000
German Cancer Research Center
1995-1996
Heidelberg University
1995-1996
To study the efficiency of RNA-based vaccines, RNA coding for model antigen beta-galactosidase (beta-gal) was transcribed in vitro from a lacZ gene flanked by stabilizing Xenopus laevis beta-globin 5' and 3' sequences protected RNase degradation condensation with polycationic peptide protamine. The liposome-encapsulated condensed RNA-peptide complex, complex without liposome or naked, unprotected RNA, injected into BALB/c (H-2(d)) mice. All preparations led to protein expression local...
To study the efficiency of RNA-based vaccines, RNA coding for model antigen beta-galactosidase (beta-gal) was transcribed in vitro from a lacZ gene flanked by stabilizing Xenopus laevis beta-globin 5' and 3' sequences protected RNase degradation condensation with polycationic peptide protamine. The liposome-encapsulated condensed RNA-peptide complex, complex without liposome or naked, unprotected RNA, injected into BALB/c (H-2(d)) mice. All preparations led to protein expression local...
For CD8(+) T cells, a relatively short antigen pulse seems sufficient for antigen-presenting cells to drive clonal expansion and differentiation. It is unknown whether the requirement similarly ephemeral CD4(+) cells. To study dependence of cell response on persistence in quantitatively temporally controlled manner vivo, we engineered mouse line expressing major histocompatibility complex class II-restricted epitope dendritic under control tetracycline-inducible promoter. Experiments...
Abstract Currently, it is not understood how the specificity of TCR guides CD4+ T cells into conventional lineage (Tconv) vs directing them to become regulatory (Treg) defined by Foxp3 transcription factor. To address this question, we made use “Limited” (LTD) mouse, which has a restricted repertoire with fixed TCRβ chain and TCRα minilocus. The repertoires Tconv Treg were equally broad, distinct, yet overlapped significantly, representing less strict partition than previously seen between...
It is currently not understood how some chronic infections exhaust antigen-specific T cells over time and which pathogen components contribute to exhaustion. Here, we dissected the behavior of primed CD4 + exposed persistent antigen using an inducible transgenic mouse system that allowed us control presentation as only experimental variable, independent inflammation disease progression complicate infectious models. Moreover, this restricted dendritic (DCs) avoided confounding B, CD8 T, or...
Abstract Prior to their association with major histocompatibility complex (MHC) class I molecules, peptides generated from cytosolic antigens need be translocated by the MHC‐encoded peptide transporter (TAP) into lumen of endoplasmic reticulum (ER). While molecules possess well‐known binding characteristics for peptides, fine specificity TAP its substrates has not been analyzed in detail. Previously, we have studied effect amino acid variations at N‐terminal, C‐terminal, and penultimate...
Activation of dendritic cells (DCs) enhances their ability to prime naïve T cells. How activation renders them immunogenic rather than tolerogenic is unclear. Here, we show, using temporally regulated expression a transgene-encoded neoself antigen in DCs, that either prolonged presentation or DC could elicit full expansion, effector cytokine production, and memory-cell differentiation. Microarray analysis gene showed all changes linked through CD40 be reproduced by persistent delivery,...
Abstract The major histocompatibility complex (MHC)‐encoded transporter associated with antigen processing (TAP) delivers cytosolic peptides to the lumen of endoplasmic reticulum (ER) for presentation by MHC class I molecules. For rat, it has been demonstrated that TAP polymorphism results in selection different sets peptides, nature C terminus being particular importance. Here, we investigated whether mice and humans functional consequences transport peptide variable at C‐terminal residues....
Abstract Ag recognition via the TCR is necessary for expansion of specific T cells that then contribute to adaptive immunity as effector and memory cells. Because CD4+ CD8+ differ in terms their priming APCs MHC ligands we compared requirements persistence during phase side by side. Proliferation differentiation transgenic polyclonal mouse were thus analyzed after transient continuous signals. Following equally strong stimulation, cell proliferation depended on prolonged presence, whereas...
Exhausted immune responses to chronic diseases represent a major challenge global health. We study CD4+ T cells in mouse model with regulatable antigen presentation. When the are driven through effector phase and then exposed different levels of persistent antigen, they lose their helper 1 (Th1) functions, upregulate exhaustion markers, resemble naturally anergic cells, modulate MAPK, mTORC1, Ca2+/calcineurin signaling pathways increasing dose time. They also become unable help B and, at...
CD8 + T cells are crucial for the clearance of viral infections. During acute phase, proinflammatory conditions increase amount circulating phosphatidylserine (PS) extracellular vesicles (EVs). These EVs interact especially with cells; however, it remains unclear whether they can actively modulate cell responses. In this study, we have developed a method to analyze cell-bound PS and their target in vivo. We show that EV abundance increases during infection preferentially bind activated, but...
By analyzing T cell responses against foreign major histocompatibility complex (MHC) molecules loaded with peptide libraries and defined self- viral peptides, we demonstrate a profound influence of self-MHC on the repertoire alloreactive cells: closer MHC molecule is related to cell's MHC, higher proportion peptide-specific, (“allorestricted”) cells versus recognizing without regard in groove. Thus, must be influenced by during positive or negative thymic selection peripheral survival, much...
Abstract The transporter associated with Ag processing (TAP) translocates cytosolic peptides into the endoplasmic reticulum for presentation by MHC class 1 molecules. Recently, actual peptide translocation step has been suggested to be preceded binding of TAP. In this study, we investigated site TAP and its relevance selection cross-linking translocatable peptides. Our data demonstrate, first, that a heterodimer containing rat TAPu allelic product, which selects on basis their C terminus,...
Abstract Mice were immunized i.p. with soluble or heat‐denatured protein antigens [ovalbumin, β‐galactosidase, recombinant E7 of human papilloma virus type 16 (HBV)]. Heat‐denatured (100°C) preparations these proteins able to induce cytotoxic T lymphocytes (CTL) that recognize cells expressing the respective genes, whereas native was either inefficient required up 30‐fold higher doses. If heat‐treated separated into aggregated and fractions by ultracentrifugation, only specific CTL; this is...
PBL from HLA-A2- or HLA-A3- donors were stimulated with synthetic peptide libraries fitting HLA-A2 HLA-A3 motifs and presented on HLA-A3-expressing TAP- cells. Peptide library-specific allorestricted CTL found to constitute up half the alloreactive response occurred at twofold lower frequency than autologous CTL. This indicates that positive selection by one particular MHC class I molecule is not absolutely essential for generation of restricted same molecule. However, increases their...
BALB/c-derived spleen cells were depleted of cytotoxic T lymphocytes (CTL) recognizing allogeneic (H2b) and TAP-negative followed by stimulation with the same loaded a synthetic library binding to H2-Kb. The resulting CTL lines found differ widely in peptide specificity exhibit an avidity towards as that demonstrated for syngeneic CTL. These results demonstrate positive selection context certain MHC molecule does not seem be required generating high-avidity TCR are restricted molecule....
Receptor–ligand interactions at cell interfaces initiate signaling cascades essential for cellular communication and effector functions. Specifically, T receptor (TCR) with pathogen-derived peptides presented by the major histocompatibility complex (pMHC) molecules on antigen-presenting cells are crucial activation. The binding duration, or dwell time, of TCR–pMHC correlates downstream efficacy, strong agonists exhibiting longer lifetimes compared to weak agonists. Traditional surface...
Receptor–ligand interactions at cell interfaces initiate signaling cascades essential for cellular communication and effector functions. Specifically, T receptor (TCR) with pathogen-derived peptides presented by the major histocompatibility complex (pMHC) molecules on antigen-presenting cells are crucial activation. The binding duration, or dwell time, of TCR–pMHC correlates downstream efficacy, strong agonists exhibiting longer lifetimes compared to weak agonists. Traditional surface...
Abstract Mechanical forces acting on ligand-engaged T-cell receptors (TCRs) have previously been implicated in antigen recognition and ligand discrimination, yet their magnitude, frequency, impact remain unclear. We quantitatively assess across various TCR:pMHC pairs with different bond lifetimes at single-molecule resolution, both before during activation, platforms that either include or exclude tangential force registration. Our results imply CD4+ TCRs experience significantly lower than...
Abstract It is currently not understood how some chronic infections exhaust antigen-specific T cells over time and different pathogen components contribute to the exhausted state. Here, we dissected behavior of primed CD4+ exposed persistent antigen using an inducible transgenic mouse system that allowed us control presentation as only experimental variable independent inflammation disease progression. In this MHC-II presented restricted dendritic so confounding B, CD8+ T, or innate cell...