- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Systemic Lupus Erythematosus Research
- Monoclonal and Polyclonal Antibodies Research
- vaccines and immunoinformatics approaches
- Multiple Sclerosis Research Studies
- Cellular transport and secretion
- Receptor Mechanisms and Signaling
- RNA Research and Splicing
- Reproductive System and Pregnancy
- Cytomegalovirus and herpesvirus research
Technical University of Denmark
2022-2024
Aarhus University
2022-2023
Abstract Circumstantial evidence suggests that B cells may instruct T to break tolerance. Here, test this hypothesis, we used a murine model in which single cell clone precipitates an autoreactive response resembling systemic lupus erythematosus (SLE). The initiating did not need enter germinal centers precipitate epitope spreading. Rather, it localized extrafollicular splenic bridging channels early the response. Autoantibody produced by was sufficient drive Subsequent spreading depended on...
Introduction Many autoimmune diseases are characterized by germinal center (GC)-derived, affinity-matured, class-switched autoantibodies, and strategies to block GC formation progression currently being explored clinically. However, extrafollicular responses can also play a role. The aim of this study was investigate the contribution pathway disease development. Methods We blocked knocking out transcription factor Bcl-6 in B cells, leaving intact. tested impact intervention two murine models...
CD8 T cells provide immunity to virus infection through recognition of epitopes presented by peptide major histocompatibility complexes (pMHCs). To establish a concise panel widely recognized cell from common viruses, we combined analysis TCR down-regulation upon stimulation with epitope-specific enumeration based on barcode-labeled pMHC multimers. We assess binding and reactivity for 929 previously reported in the context 1 25 HLA alleles representing 29 viruses. The prevalence magnitude...
Abstract Objective Anti‐CD20 therapy is a highly effective treatment for multiple sclerosis (MS). In this study, we investigated MS‐related changes in peripheral blood mononuclear cell (PBMC) subsets compared to healthy controls and longitudinal related the treatment. Methods Multicolor spectral flow cytometry analysis was performed on 78 samples characterize disease‐ treatment‐related PBMC clusters. Blood from MS patients were collected at baseline up 8 months post‐treatment, with three...
The Vps10p domain receptor SorCS2 is crucial for the development and function of nervous system essential brain-derived neurotrophic factor (BDNF)-induced changes in neuronal morphology plasticity. regulates subcellular trafficking BDNF signaling TrkB as well selected neurotransmitter receptors a manner that dependent on intracellular (ICD). However, cellular machinery adaptor protein (AP) interactions regulate via ICD are unknown. We here identify four splice variants human differing...
Abstract Many autoimmune diseases are characterized by germinal center (GC) derived affinity-matured, class-switched autoantibodies. Strategies to block GC formation and progression currently being explored clinically, however, extrafollicular responses may also contribute early events in autoimmunity. To investigate the relative contribution of these two pathways disease development, we leveraged a transgenic strategy genetically pathway. Surprisingly, this accelerated failed curb lupus...
A progressive increase in the breadth and specificity of autoantibodies over time, termed epitope spreading, drives pathogenic targeting an ever-widening repertoire self-components many autoimmune diseases. Ostensibly, this inclusion additional B cell clones into ongoing autoreactive response can occur through linked recognition, whereby proto-autoreactive cells recognize distinct antigenic epitopes, which carry shared T epitopes. In a murine model displaying spreading resembling that...
Introduction MHC class II molecules are essential for appropriate immune responses against pathogens but also implicated in pathological autoimmune diseases and transplant rejection. Previous studies have shed light on the systemic contributions of haplotypes to development severity diseases. In this study, we addressed B cell intrinsic haplotype impact follicular inclusion, germinal center (GC) participation plasma (PC) differentiation context lupus erythematosus (SLE). Methods We leveraged...
Abstract Knowledge of widely recognized T-cell epitopes against common virus infections are vital for immune monitoring and characterization relevant antigen-specific CD8 T cells their antigen receptors. We therefore aimed to establish a concise validated epitope panel human virus-specific immunity complete with data on both prevalence recognition reactivity in humans. To achieve this, we first TCR downregulation, loss peptide major histocompatibility (pMHC) multimer-binding, as an early...