A5035934082- Hepatitis C virus research
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- SARS-CoV-2 and COVID-19 Research
- Hepatitis B Virus Studies
- vaccines and immunoinformatics approaches
- Immunotherapy and Immune Responses
- Diabetes and associated disorders
- COVID-19 Clinical Research Studies
- Hepatitis Viruses Studies and Epidemiology
- Viral Infections and Immunology Research
- Liver Disease Diagnosis and Treatment
- Liver Diseases and Immunity
- Cytomegalovirus and herpesvirus research
- Cancer Immunotherapy and Biomarkers
- Genetics and Neurodevelopmental Disorders
- Immunodeficiency and Autoimmune Disorders
- Cancer, Hypoxia, and Metabolism
- Systemic Lupus Erythematosus Research
- Exercise and Physiological Responses
- COVID-19 epidemiological studies
- CAR-T cell therapy research
- Mitochondrial Function and Pathology
- Vibrio bacteria research studies
- ATP Synthase and ATPases Research
University Medical Center Freiburg
2016-2025
University of Freiburg
2017-2025
Technical University of Denmark
2023-2024
SARS-CoV-2 spike mRNA vaccines
Abstract Differentiation and fate of virus-specific CD8 + T cells after cessation chronic antigen stimulation is unclear. Here we show that a TCF1 CD127 PD1 hepatitis C virus (HCV)-specific T-cell subset exists in chronically infected patients with phenotypic features exhaustion memory, both before treatment direct acting antiviral (DAA) agents. This maintained during, for long duration after, HCV elimination. After re-challenge the less differentiated population expands, which accompanied...
The origin of SARS-CoV-2 variants concern remains unclear. Here, we test whether intra-host virus evolution during persistent infections could be a contributing factor by characterizing the long-term infection dynamics in an immunosuppressed kidney transplant recipient. Applying RT-qPCR and next-generation sequencing (NGS) sequential respiratory specimens, identify several mutations viral genome late infection. We demonstrate that isolate exhibiting similar to those found first identified...
Objective A hallmark of chronic HBV (cHBV) infection is the presence impaired HBV-specific CD8+ T cell responses. Functional exhaustion induced by persistent antigen stimulation considered a major mechanism underlying this impairment. However, due to their low frequencies in infection, it currently unknown whether cells targeting different epitopes are similarly and share molecular profiles indicative exhaustion. Design By applying peptide-loaded MHC I tetramer-based enrichment, we could...
Primary antibody deficiencies (PADs) are the most frequent primary immunodeficiencies in human subjects. The genetic causes of PADs largely unknown. Sec61 translocon alpha 1 subunit (SEC61A1) is major complex, which main polypeptide-conducting channel endoplasmic reticulum membrane. SEC61A1 a target gene spliced X-box binding protein and strongly induced during plasma cell (PC) differentiation.We identified novel defect studied its pathologic mechanism 11 patients from 2 unrelated families...
Oncogenic KRAS mutations drive metabolic rewiring in pancreatic ductal adenocarcinoma (PDAC). Src-homology 2 domain-containing phosphatase (SHP2) is essential for full activity and promising dual SHP2/mitogen-activated protein kinase (MAPK) inhibition currently being tested clinical trials. Exploitable adaptations may contribute to an invariably evolving resistance. To understand the changes induced by inhibition, we comprehensively cell lines, endogenous tumor models, patient-derived...
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...
Endoplasmic reticulum aminopeptidase 1 (ERAP1) polymorphisms are linked with human leukocyte antigen (HLA) class I-associated autoinflammatory disorders, including ankylosing spondylitis and Behçet's disease. Disease-associated ERAP1 allotypes exhibit distinct functional properties, but it remains unclear how differential peptide trimming in vivo affects the repertoire of epitopes presented to CD8+ T cells. The aim this study was determine impact on virus-specific cell epitope an...
Abstract CD8+ T cells are critical for the elimination and long-lasting protection of many viral infections, but their role in current SARS-CoV-2 pandemic is unclear. Emerging data indicates that SARS-CoV-2-specific detectable majority individuals recovering from infection. However, optimal virus-specific epitopes, pre-existing heterologous immunity as well kinetics differentiation program during disease control have not been defined detail. Here, we show both newly induced T-cell responses...
Abstract The recent emergence of SARS-CoV-2 variants showing increased transmissibility and immune escape is a matter global concern. Their origin remains unclear, but intra-host virus evolution during persistent infections could be contributing factor. Here, we studied the long-term infection in an immunosuppressed organ transplant recipient. Frequent respiratory specimens were tested for variant viral genomes by RT-qPCR, next-generation sequencing (NGS), isolation. Late infection, several...
Abstract SARS-CoV-2 spike mRNA vaccines mediate protection from severe disease as early 10 days post prime vaccination, when specific antibodies are hardly detectable and still lack neutralizing activity. Vaccine-induced T cells, especially CD8+ may thus be the main mediators of at this stage. The details antigen-specific cell induction after prime/boost their comparison to naturally induced responses association with other arms vaccine-induced adaptive immunity remain, however, incompletely...
<h3>Background</h3> Exercise enhances immunosurveillance and prevents development recurrence of a variety cancer types. It has been well studied that acute exercise induces mobilization lymphocytes into the peripheral blood, predominantly comprising NK cells antigen-experienced T cells. The mechanisms underlying clinical benefits in patients are still unclear. Substantial aspects like antigen specificity exercise-mobilized or secreted markers have only recently attracted research attention....
Hepatitis C virus (HCV) infections can manifest as acute-spontaneously resolving or chronic, with CD8+T cells (CTLs) playing a pivotal role in disease outcome. While extensive research focused on exhaustion of virus-specific CTLs chronic HCV infection, the characterization protective CTL responses has been understudied recent years. Moreover, past investigations primarily prevalent European HLA allele HLA-A*02:01 when exploring distinctive phenotypes HCV-specific versus spontaneously...
Background/aim: In hepatitis C virus (HCV) infection, HLA-B*27 is associated with spontaneous viral clearance of acute infection. However, some HLA-B*27+ patients develop chronic HCV infection due to an inefficient HCV-specific immune response. order determine factors influencing this course we comprehensively characterized HLA*B27+ patient who controlled the low titers close limit detection but did not completely clear for > 12 months.
Chronic Hepatitis C virus (HCV) infection results in impaired HCV-specific CD8+ T-cell responses, a phenomenon called exhaustion. Exhausted T cells exhibit reduced cytokine production and proliferative capacity, co-express inhibitory molecules (e.g. PD-1) lack memory markers like IL-7R a-chain (CD127) or transcription factor TCF1. The mechanisms responsible for exhaustion are not completely understood, however, one key feature seems to be the prolonged continuous exposure antigen. In chronic...
Chronic viral infections like Hepatitis C virus (HCV) and Human immunodeficiency (HIV) lead to considerable morbidity mortality worldwide. HIV/HCV coinfection is very common among certain risk groups has significant clinical therapeutical impacts, e.g. faster progression of HCV-related liver disease compared HCV monoinfection. Immunologically, the persistent antigen exposure in both chronic HIV infection induces CD8+ T-cell exhaustion that characterized by impaired functional capacity...
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...
Das Hepatitis-E-Virus (HEV) ist eine der Hauptursachen einer Virushepatitis weltweit. In immunkompetenten Individuen heilt HEV-Infektion spontan aus, Immunsuppression hingegen kann zu einem chronischen Verlauf bis zur Leberzirrhose und Hepatozellulärem Karzinom führen.
Hepatitis E Virus (HEV) infection is one of the leading causes viral hepatitis worldwide. Immune competent individuals clear spontaneously, whereas in immune suppressed patients chronic can occur, ultimately to liver cirrhosis and Hepatocellular Carcinoma (HCC).