A5001814779- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Glycosylation and Glycoproteins Research
- T-cell and B-cell Immunology
- Hepatitis C virus research
- Systemic Lupus Erythematosus Research
- Blood groups and transfusion
- Galectins and Cancer Biology
- vaccines and immunoinformatics approaches
- Platelet Disorders and Treatments
- Immune Cell Function and Interaction
- Hepatitis B Virus Studies
- Blood disorders and treatments
- Peptidase Inhibition and Analysis
- Click Chemistry and Applications
- Erythrocyte Function and Pathophysiology
- Blood transfusion and management
- Rheumatoid Arthritis Research and Therapies
- Chronic Lymphocytic Leukemia Research
- European Socioeconomic and Political Studies
- CAR-T cell therapy research
- Liver Diseases and Immunity
- Hepatitis Viruses Studies and Epidemiology
- Multiple and Secondary Primary Cancers
Sanquin
2013-2024
Leiden University
1997-2003
Leiden University Medical Center
1998-2002
Glycosylation of the immunoglobulin G (IgG)-Fc tail is required for binding to Fc-gamma receptors (FcγRs) and complement-component C1q. A variety IgG1 glycoforms detected in human sera. Several groups have found global or antigen specific skewing IgG glycosylation, example autoimmune diseases, viral infections, alloimmune reactions. The glycoprofiles seem correlate with disease outcome. Additionally, IgG-glycan composition contributes significantly Ig based therapies, as IVIg diseases...
Major histocompatibility complex (MHC) class I multimer technology has become an indispensable immunological assay system to dissect antigen-specific cytotoxic CD8(+) T cell responses by flow cytometry. However, the development of high-throughput systems, in which against a multitude epitopes are analyzed, been precluded fact that for each epitope, separate vitro MHC refolding reaction is required. We have recently demonstrated conditional ligands disintegrate upon exposure long-wavelength...
Immunoglobulins G (IgG) and their Fc gamma receptors (FcγRs) play important roles in our immune system. The conserved N-glycan the region of IgG1 impacts interaction IgG with FcγRs resulting effector functions, which has led to design antibody therapeutics greatly improved antibody-dependent cell cytotoxicity (ADCC) activities. Studies have suggested that also N-glycosylation FcγRIII affects receptor interactions IgG, but detailed studies FcγRIIIa distinct N-glycans been hindered by natural...
Immunoglobulin G (IgG) antibodies are important for protection against pathogens and exert effector functions through binding to IgG-Fc receptors (FcγRs) on myeloid natural killer cells, resulting in destruction of opsonized target cells. Despite interspecies differences, IgG subclasses FcγRs show substantial similarities functional conservation between mammals. Accordingly, human (hIgG) mouse (mFcγRs) has been utilized study hIgG mice. In other applications, such as immunostaining with...
Approximately 20% of patients receiving multiple platelet transfusions develop alloantibodies, which can be directed against human leukocyte antigens (HLA) and, to a lesser extent, (HPA). These antibodies lead the rapid clearance donor platelets, presumably through IgG-Fc receptor (FcγR)-mediated phagocytosis or via complement activation, resulting in refractoriness. Strikingly, not all with anti-HLA -HPA refractoriness upon unmatched transfusions. Previously, we found that IgG Fc...
Immunoglobulin G (IgG) antibodies serve a crucial immuno-protective function mediated by IgG Fc receptors (FcγR). Absence of fucose on the highly conserved N-linked glycan in domain strongly enhances binding and activation myeloid natural killer (NK) cell FcγRs. Although afucosylated can provide increased protection (malaria HIV), it also boosts immunopathologies alloimmune diseases, COVID-19 dengue fever. Quantifying fucosylation currently requires sophisticated methods such as liquid...
To understand the regulation of rheumatoid factor (RF) production in arthritis (RA), we studied IgM-RF by B cells isolated from synovial fluid (SF).Highly purified SF and peripheral blood (PB) were negative selection a fluorescence-activated cell sorter (FACS) then cultured with either L cells, CD40 ligand (CD40L)-transfected or type synoviocytes presence absence interleukin-2 (IL-2), IL-4, IL-10. Total IgM detected after 14 days enzyme-linked immunosorbent assay. Enzyme-linked immunospot...
Bioorthogonal cleavable linkers are attractive building blocks for compounds that can be manipulated to study biological and cellular processes. Sodium dithionite sensitive azobenzene-containing (Abc) peptides were applied the temporary stabilization of recombinant MHC complexes, which then employed generate libraries tetramers after exchange with a novel epitope. This technology represents an important tool high-throughput studies disease-specific T cell responses.
The binding strength between IgG and FcγR is influenced by the composition of N-linked glycan at position N297 in Fc-domain IgG. Particularly, afucosylation increases affinity human IgG1 to FcγRIIIa up ∼20 fold, additional galactosylation afucosylated ∼40 fold. increase for has previously been shown depend on direct carbohydrate-carbohydrate interactions IgG-Fc with an 162 unique hFcγRIIIa hFcγRIIIb. Here we report that N162 glycosylation site also found orthologous mouse FcγR, mFcγRIV....
Abstract Neonatal Fc-receptor (FcRn), the major histocompatibility complex (MHC) class I-like Fc-receptor, transports immunoglobuline G (IgG) across cell layers, extending IgG half-life in circulation and providing newborns with humoral immunity. IgG1 IgG2 have similar half-lives, yet displays lower foetal than maternal concentration at term, despite all known FcRn binding residues being preserved between IgG2. We investigated mediated transcytosis of V H -matched mutated variants thereof...
ABSTRACT Virus-specific CD8 T cell response seems to play a significant role in the outcome of hepatitis delta virus (HDV) infection. However, HDV-specific epitope repertoire and mechanisms failure HDV infection have been poorly characterized. We therefore aimed characterize epitopes impacts viral mutations on immune escape. In this study, we predicted peptide binding most frequent human leukocyte antigen (HLA) types assessed their HLA capacities. These were characterized HDV-infected...
Identification of immunogenic cancer neoantigens as targets for therapy is challenging. Here, we integrate the whole-genome and long-read transcript sequencing cancers to identify collection neo-open reading frame peptides (NOP) expressed in tumors. We termed this NOPs tumor framome. represent tumor-specific that are different from wild-type proteins may be strongly immunogenic. describe a class hidden derive structural genomic variants involving an upstream protein coding gene driving...
The formation of alloantibodies directed against class I human leukocyte antigens (HLA) continues to be a clinically challenging complication after platelet transfusions, which can lead refractoriness (PR) and occurs in approximately 5%-15% patients with chronic support. Interestingly, anti-HLA IgG levels alloimmunized do not seem predict PR, suggesting functional or qualitative differences among IgG. binding these donor platelets result rapid clearance transfusion, presumably via...
Antibody-mediated blood disorders ensue after auto- or alloimmunization against cell antigens, resulting in cytopenia. Although the mechanisms of destruction are same as immunotherapies targeting tumor cells, many factors still unknown. Antibody titers, for example, often do not strictly correlate with clinical outcome. Previously, we found C-reactive protein (CRP) levels to be elevated thrombocytopenic patients, correlating thrombocyte counts, and bleeding severity. Functionally, CRP...
ABSTRACT CD8 + T cells are an essential component of successful adaptive immune responses against hepatitis C virus (HCV). A major obstacle to vaccine design HCV is its inherent viral sequence diversity. Here, we test the hypothesis that different variants immunodominant cell epitope, all binding with high affinity HLA class I, target receptor repertoires and thereby influence quality response. The impacts differences in HLA-A*02-restricted NS3 1406–1415 epitope on vitro priming naive from...
Abstract Peptide–MHC (pMHC) multimers have become one of the most widely used tools to measure Ag-specific T cell responses in humans. With aim understanding requirements for pMHC-based personalized immunomonitoring, which individuals expressing subtypes commonly studied HLA alleles are encountered, we assessed how ability detect cells a given peptide is affected by micropolymorphic differences between subtypes. First, analysis set 10 HLA-A*02:01–restricted clones demonstrated that staining...
Immunotherapy represents an attractive option for the treatment of chronic hepatitis B virus (HBV) infection. The HBV proteins polymerase (Pol) and HBx are special interest antigen-specific immunotherapy because they essential viral replication have been associated with control or still expressed upon DNA integration (HBx). Here, we scored all currently described HBx- Pol-derived epitope sequences indispensability conservation across genotypes. This yielded 7 HBx-derived 26 reported epitopes...
SUMMARY The persistent presence of rheumatoid factors (RFs) in the circulation is a characteristic phenomenon patients with arthritis (RA). Recent data indicate that RFs associated seropositive RA are derived from terminally differentiated CD20–, CD38+ plasma cells (PCs) present synovial fluids inflamed joints. These were shown to secrete actively and thought originate germinal centre (GC)-like structures synovium. To obtain representative image structural properties IgM IgG RA, phage...
Abstract Transfusion-related acute lung injury (TRALI) remains a leading cause of transfusion-related deaths. In most cases, anti-leukocyte antibodies in the transfusion product trigger TRALI, but not all TRALI. It has been shown that anti–major histocompatibility complex (MHC) class I antibody 34-1-2S (anti–H-2Kd) causes TRALI BALB/c mice (MHC haplotype H-2Kd), whereas SF1.1.10 does not. C57BL/6 H-2Kb), only occurs when anti-MHC AF6-88.5.5.3 (anti–H-2Kb) is administered together with high...
Abs of the IgG isotype mediate effector functions like Ab-dependent cellular cytotoxicity and phagocytosis by Fc interactions with FcγRs complement-dependent upon IgG-Fc binding to C1q. In this study, we describe crucial role highly conserved dual glycines at position 236-237 in lower hinge region human IgG, including lack one glycine as found IgG2. We several permutations that either silence or largely abrogate FcγR downstream functions, demonstrated surface plasmon resonance, phagocytosis,...
Summary Rheumatoid factors (RFs) are autoantibodies directed against the Fc part of IgG. Considerable evidence exists that there two classes RFs, pathological and physiological. Whereas RFs associated with disease, physiological considered to be a normal component immune response. RF+ precursor B cells present as cell repertoire healthy individuals held responsible for production which is transient phenomenon clear correlation an initiating stimulus such immunization or exposure infection....