A5071410670- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunodeficiency and Autoimmune Disorders
- Immune Response and Inflammation
- Trypanosoma species research and implications
- RNA Interference and Gene Delivery
- Monoclonal and Polyclonal Antibodies Research
- Cell death mechanisms and regulation
- Cell Adhesion Molecules Research
- Cytomegalovirus and herpesvirus research
- Synthesis and Biological Evaluation
- NF-κB Signaling Pathways
- interferon and immune responses
- Peptidase Inhibition and Analysis
- Chronic Lymphocytic Leukemia Research
- RNA regulation and disease
- Vasculitis and related conditions
- Pancreatic function and diabetes
- Toxin Mechanisms and Immunotoxins
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Phagocytosis and Immune Regulation
- RNA and protein synthesis mechanisms
- Chemical Synthesis and Analysis
- Computational Drug Discovery Methods
- Ubiquitin and proteasome pathways
University Medical Center Freiburg
2014-2024
University of Freiburg
2018-2024
Bariloche Atomic Centre
2019-2024
Consejo Nacional de Investigaciones Científicas y Técnicas
2007-2024
Comisión Nacional de Energía Atómica
2019-2024
University of Lausanne
2012-2022
Universidad Nacional de Cuyo
2021
Balseiro Institute
2019
Immunologie, Immunopathologie et Chimie Thérapeutique
2010-2017
Institut de Biologie Moléculaire et Cellulaire
2010-2017
Cytotoxic T lymphocyte antigen-4 (CTLA-4) limits T-cell activation and is expressed on T-regulatory cells. Human CTLA-4 deficiency results in severe immune dysregulation. Abatacept (CTLA-4 Ig) approved for the treatment of rheumatoid arthritis (RA) its mechanism action attributed to effects T-cells. It known that modulates expression ligands CD80 CD86 antigen presenting cells (APC) by transendocytosis. As B-cells express CD80/CD86 function as APC, we hypothesize are a direct target...
B cell activating factor (BAFF) provides cells with essential survival signals. It binds to three receptors: BAFFR, TACI, and BCMA that are differentially expressed by subsets. BAFFR is early in circulating key signals for further maturation. Here, we report highly regulated processing events modulate BAFF responses. triggered binding co-expressing TACI it executed the metalloproteases ADAM10 ADAM17. The degree of oligomerization, expression ADAM proteins different subsets, activation status...
B-cell depletion time after rituximab (RTX) treatment is prolonged in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) compared with other autoimmune diseases. We investigated central and peripheral development to identify the causes for defect reconstitution RTX therapy.
Defective FAS (CD95/Apo-1/TNFRSF6) signaling causes autoimmune lymphoproliferative syndrome (ALPS). Hypergammaglobulinemia is a common feature in ALPS with mutations (ALPS-FAS), but paradoxically, fewer conventional memory cells differentiate from FAS-expressing germinal center (GC) B cells. Resistance to FAS-induced apoptosis does not explain this phenotype. We tested the hypothesis that defective non-apoptotic may contribute impaired cell differentiation ALPS. analyzed secondary lymphoid...
Common variable immunodeficiency (CVID) is the most frequent symptomatic primary immunodeficiency. Patients with CVID are prone to recurrent bacterial infection due failure of adequate immunoglobulin production. Monogenetic defects have been identified in approximately 25% patients. Recently, mutations IKZF1, encoding zinc-finger transcription factor IKAROS which broadly expressed hematopoietic cells, associated a CVID-like phenotype. Herein we describe eleven patients heterozygous IKZF1...
Summary Chronic Chagas heart disease (cChHD), a chronic manifestation of the Trypanosoma cruzi infection, is characterized by high antibody levels against C-terminal region ribosomal P proteins (i.e. peptide R13, EEEDDDMGFGLFD) which bears similarity with second extracellular loop β1-adrenergic receptor (β1-AR, H26R HWWRAESDEARRCYNDPKCCDFVTNR). Because it has not been demonstrated clearly that IgGs from cChHD patients bind to native human β1-AR, aim this study was investigate further...
In a classical dogma, pathogens are sensed (via recognition of Pathogen Associated Molecular Patterns (PAMPs)) by innate immune cells that in turn activate adaptive cells. However, recent data showed TLRs (Toll Like Receptors), the most characterized class Pattern Recognition Receptors, also expressed B play an important role protective immunity essentially differentiating into antibody-secreting (ASC). This differentiation requires at least two signals: antigen cell specific receptor (BCR)...
Abstract We have developed a straightforward strategy to multimerize an apoptogenic peptide that mimics the natural tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) by using adamantane‐based dendrons as multivalent scaffolds. The selective binding affinity of ligands TRAIL receptor 2 (TR2) was studied surface plasmon resonance, thus demonstrating trimeric and hexameric forms exert increased about 1500‐ 20 000‐fold, respectively, relative monomer. Moreover, only were able...
Abstract Controlling the covalent bonding of antibodies onto functionalized carbon nanotubes is a key step in design and preparation nanotube‐based conjugates for targeting cancer cells. For this purpose, an anti‐MUC1 antibody (Ab) linked to both multi‐walled (MWCNTs) double‐walled (DWCNTs) using different synthetic strategies. The presence Ab attached confirmed by gel electrophoresis thermogravimetric analysis. Most importantly, molecular recognition antigen surface plasmon resonance able...
Abstract The B cell survival factor (TNFSF13B/BAFF) is often elevated in autoimmune diseases and targeted the clinic for treatment of systemic lupus erythematosus. BAFF contains a loop region designated flap, which dispensable receptor binding. Here we show that flap has two functions. In addition to facilitating formation highly active 60-mer as shown previously, it also converts binding TNFRSF13C (BAFFR) into signaling event via oligomerization individual BAFF-BAFFR complexes. Binding...
The activation of CD40 on B cells, macrophages, and dendritic cells by its ligand CD154 (CD40L) is essential for the development humoral cellular immune responses. CD40L other TNF superfamily ligands are noncovalent homotrimers, but form under which exists in absence remains to be elucidated. Here, we show that both cell surface-expressed soluble self-assemble, most probably as dimers. cysteine-rich domain 1 (CRD1) participated dimerization was also required efficient receptor expression....
Abstract TNF receptor superfamily members (TNFRSF) such as CD40, Fas and TRAIL 2 (TRAILR2) participate to the adaptive immune response by eliciting survival, proliferation, differentiation and/or cell death signals. The balance between these signals determines fate of response. It was previously reported that receptors are able self-assemble in absence ligand through their extracellular regions. However, role this oligomerization is not well understood, none proposed hypotheses take into...
In mature B cells, TACI controls class-switch recombination and differentiation into plasma cells during T cell-independent antibody responses. binds the ligands BAFF APRIL. Approximately 10% of patients with common variable immunodeficiency (CVID) carry mutations, which A181E C172Y are in transmembrane domain. Residues A181 C172 located on distinct sides helix, is predicted by molecular modeling to spontaneously assemble trimers dimers. human these mutations impair ligand-dependent (C172Y)...
Binding of BAFF to BAFFR activates in mature B cells PI3K/AKT signaling regulating protein synthesis, metabolic fitness, and survival. In humans, naive memory express the same levels BAFFR, but only seem survive without BAFF. Here, we show that changes expression genes migration, proliferation, growth, BAFF-induced activation requires direct interactions between cell antigen receptor (BCR) components CD79A CD79B is enhanced by AKT coactivator TCL1A. Compared cells, more surface BCRs, which...
The maintenance of B cell homeostasis requires a tight control generation, survival, activation, and maturation. In lymphocytes upon increased sensitivity to apoptotic signals helps controlling differentiation proliferation. death receptor Fas is important in this context because genetic mutations humans lead an autoimmune lymphoproliferative syndrome that similar lymphoproliferation observed Fas-deficient mice. contrast, the physiological role TNF-related apoptosis-inducing ligand receptors...
Abstract Intercellular communication is crucial for collective regulation of cellular behaviors. While clustering T cells have been shown to mutually control the production key signals, it unclear whether they also jointly regulate their availability and degradation. Here we use newly developed reporter systems, bioinformatic analyses, protein structure modeling genetic perturbations assess this. We find that utilize trogocytosis by competing antagonistic receptors differentially abundance...
Antibodies from patients with Chagas heart disease and monoclonal antibodies (or mAb) to the carboxy-terminal end (B cell epitope R13) of ribosomal P2beta protein Trypanosoma cruzi (TcP2beta) cross-react beta1 adrenergic receptor (beta1-AR). Two single-chain Fv fragments (scFv) C5 B7 derived variable regions anti-R13 mAb 17.2 were expressed. scFv was a dimer bound TcP2beta an affinity K(d) = 8 nM, whereas monomeric had less than for TcP2beta, 46 nM. The constant second extracellular loop...
B cell activating factor of the TNF family (BAFF), also known as lymphocyte stimulator, is a ligand required for generation and maintenance lymphocytes. In this study, ability different monoclonal antibodies to recognize, inhibit, or activate mouse BAFF was investigated. One them, IgG1 named Sandy-2, prevented binding all its receptors, receptor, transmembrane activator calcium modulating interactor, maturation antigen, at stoichiometric ratio; blocked activity on variety cell-based reporter...