A5035823763- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Monoclonal and Polyclonal Antibodies Research
- Mitochondrial Function and Pathology
- vaccines and immunoinformatics approaches
- Immune cells in cancer
- RNA and protein synthesis mechanisms
- Glycosylation and Glycoproteins Research
- RNA modifications and cancer
- Metabolism and Genetic Disorders
- Viral Infections and Immunology Research
- Endoplasmic Reticulum Stress and Disease
- RNA Research and Splicing
- Ubiquitin and proteasome pathways
- Cancer Immunotherapy and Biomarkers
- Systemic Lupus Erythematosus Research
- Rheumatoid Arthritis Research and Therapies
- Diabetes and associated disorders
- Pancreatic function and diabetes
- interferon and immune responses
- RNA Interference and Gene Delivery
- Cell Adhesion Molecules Research
- Peptidase Inhibition and Analysis
- Adipose Tissue and Metabolism
Netherlands Metabolomics Centre
2015-2025
Leiden University Medical Center
2016-2025
Leiden University
1992-2023
Janssen (Netherlands)
2013
Institute of Haematology and Blood Transfusion
2011
Cleveland Clinic
1998
Autoimmune responses against posttranslationally modified antigens are a hallmark of several autoimmune diseases. For example, antibodies citrullinated protein (ACPA) have shown their relevance for the prognosis and diagnosis rheumatoid arthritis (RA), been implicated in disease pathogenesis. It is conceivable that other autoantibody systems, recognizing proteins, also present RA. Here, we describe presence an system discriminates between citrulline- homocitrulline-containing sera...
Abstract RNA viruses encode an RNA-dependent polymerase (RdRp) that catalyzes the synthesis of their RNA(s). In case positive-stranded belonging to order Nidovirales, RdRp resides in a replicase subunit is unusually large. Bioinformatics analysis this non-structural protein has now revealed nidoviral signature domain (genetic marker) N-terminally adjacent and no apparent homologs elsewhere. Based on its conservation profile, proposed have nucleotidylation activity. We used recombinant 9...
The efficiency of antigen ( A g) processing by dendritic cells DC s) is vital for the strength ensuing T ‐cell responses. Previously, we and others have shown that in comparison to protein vaccines, vaccination with synthetic long peptides SLP has more promising (pre‐)clinical results. Here, studied unknown mechanisms underlying observed vaccine efficacy s. We report an vitro analysis s MHC class I II presentation murine human monocyte‐derived Compared protein, were rapidly much efficiently...
Objectives To understand the molecular features distinguishing anti-citrullinated protein antibodies (ACPA) from ‘conventional’ in rheumatoid arthritis (RA). Methods Serum of ACPA-positive RA patients was fractionated by size exclusion chromatography and analysed for presence ACPA-IgG ELISA. non-citrulline-specific IgG were affinity purified serum, plasma and/or synovial fluid gel electrophoresis. Electrophoresis bands excised, enzymatically digested mass spectrometry. Binding to...
Certain cytotoxic chemotherapeutic drugs are immunogenic, stimulating tumor immunity through mechanisms that not completely understood. Here we show how the DNA-damaging drug cisplatin modulates immunity. At maximum tolerated dose (MTD), cured 50% of mice with established murine TC-1 or C3 tumors, which preclinical models human papillomavirus (HPV)-associated cancer. Notably, curative benefit relied entirely upon induction tumor-specific CD8+ T cells. Mechanistic investigations showed...
Significance MHC class I molecules select and present a limited set of peptides from broad repertoire provided by TAP. How makes this selection is unclear. We show that H-2K b initially bind many because highly flexible binding pockets. Peptide followed step wherein large fraction these released, leaving the canonical for presentation. The peptide presentation has remarkable temperature dependency explains low-affinity found associated to in cells cultured at low temperature. Our data...
Membrane contact sites (MCS) are intracellular regions where two organelles come closer to exchange information and material. The majority of the endoplasmic reticulum (ER) MCS attributed ER-localized tether proteins VAPA, VAPB, MOSPD2. These recruit other ER by interacting with their FFAT motifs. Here, we describe MOSPD1 MOSPD3 as tethers motif-containing proteins. Using BioID, identify VAP MOSPD find that prefer unconventional FFAT-related FFNT (two phenylalanines [FF] in a neutral tract)...
The guanine nucleotide exchange factor, elongation factor 1 beta gamma (EF-1 gamma) has been purified from Artemia cysts using an improved method. protein consists of two distinct polypeptides with relative molecular masses 26,000 beta) and 46,000 gamma). A nucleoside diphosphate phosphotransferase activity often found in EF-1 preparations completely separated the actual stimulatory gamma, thus indicating that is not intrinsic property beta. Both have shown to stimulate following three...
The murine MC-38 colorectal cancer model is a commonly used for with high mutational burden, which sensitive immune checkpoint immunotherapy. We set out to analyze endogenous CD8+ T cell responses neo-antigens in tumor-bearing mice and after anti-PD-L1 therapy. Through combination of whole-exome sequencing analysis mass spectrometry MHC class I eluted peptides we could identify eight candidate epitopes. Of these, neo-epitope encoded by point-mutation the sequence ribosomal protein L18...
Many reagents have emerged to study the function of specific enzymes in vitro. On other hand, target are scarce or need improvement, allowing investigations individual their native cellular context. Here we report development a target-selective fluorescent small-molecule activity-based DUB probe that is active live cells and an vivo animal model. The labels ubiquitin carboxy-terminal hydrolase L1 (UCHL1), also known as neuron-specific protein PGP9.5 (PGP9.5) Parkinson disease 5 (PARK5),...
ABSTRACT The eukaryotic elongation factor-1 (EF-1) consists of four subunits, EF-1α, EF-1β, EF-1γ and EF-1d which induce efficient transfer aminoacyltRNA to the ribosome. In this process EF-1α·GTP acts as carrier on its way After release ribosome under concomitant hydrolysis GTP, inactive EF-1α·GDP form is recycled by EF-1βγd. cells concentration EF-1α exceeds that complex βγd a factor 5-10. order delineate intracellular localization different subunits EF-1, antibodies against EF-1 have been...
An equilibrium isotope exchange technique was used to measure in an Artemia system the catalytic influence of elongation factor (EF) 1 beta gamma on dissociation GDP from complex alpha.[3H] presence excess free GDP. The kinetic data demonstrate that, analogy procaryotes, occurs via formation a transient ternary EF-1 alpha.GDP.EF-1 gamma. rate constants for alpha.GDP and were found be 0.7 x 10(-3) greater than or equal s-1, respectively. association alpha.EF-1 2.3 10(5) 4.2 M-1, Judged known...
Elongation factor 1 beta (EF-1 beta) from Artemia is phosphorylated to a high percentage at serine 89 by an endogenous kinase present in EF-1 gamma. Protein sequencing of revealed that this residue located N-terminally acidic cluster amino acids, (formula; see text) which critical for casein II-type substrate recognition. A number compounds known influence kinases were studied, revealing the activity as gamma belongs class II. The rate nucleotide exchange on alpha catalyzed was found be...
HLA-DQ2 and HLA-DQ8 are strongly predisposing haplotypes for type 1 diabetes (T1D). Yet HLA-DQ2/8 heterozygous individuals have a synergistically increased risk compared with or homozygote subjects that may result from the presence of transdimer formed between α-chain (DQA1*05:01) β-chain (DQB1*03:02). We generated cells exclusively expressing this (HLA-DQ8trans), characterized its peptide binding repertoire, defined unique transdimer-specific motif was found to be distinct those HLA-DQ8....
Significance Refractory celiac disease type II (RCDII) is a severe variant of disease, an autoimmune disorder the small intestine caused by inflammatory T-cell responses to gluten, common food protein. Typical RCDII presence aberrant lymphocytes in duodenal epithelium, which often give rise lethal lymphoma. A single growth factor promoting expansion cells has been identified: epithelial cell-derived IL-15. The experiments described this paper identify three additional factors—TNF, IL-2, and...
Autoantibodies against post-translationally modified proteins (anti-modified protein antibodies or AMPAs) are a hallmark of rheumatoid arthritis (RA). A variety classes AMPAs different modifications on proteins, such as citrullination, carbamylation and acetylation, have now been described in RA. At present, there is no conceptual framework explaining the concurrent presence mutual relationship AMPA responses Here, we aimed to gain understanding co-occurrence by postulating that response...