A5039015867- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Single-cell and spatial transcriptomics
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Neuroinflammation and Neurodegeneration Mechanisms
- Immune Response and Inflammation
- vaccines and immunoinformatics approaches
- Blood groups and transfusion
- Autoimmune Neurological Disorders and Treatments
- Immunodeficiency and Autoimmune Disorders
- SARS-CoV-2 and COVID-19 Research
- Monoclonal and Polyclonal Antibodies Research
ETH Zurich
2021-2024
The mechanisms underlying the chronicity of autoimmune diseases central nervous system (CNS) are largely unknown. In particular, it is unclear whether tissue-resident memory T cells (T RM ) contribute to lesion pathogenesis during chronic CNS autoimmunity. Here, we observed that a high frequency brain-infiltrating CD8 + exhibit -like phenotype in human encephalitis. Using mouse models neuronal autoimmunity and combination single-cell transcriptomics, high-dimensional flow cytometry,...
In chronic inflammatory diseases of the central nervous system (CNS), immune cells persisting behind blood-brain barrier are supposed to promulgate local tissue destruction. The drivers such compartmentalized inflammation remain unclear, but tissue-resident memory T (TRM) represent a potentially important cellular player in this process. Here, we investigated whether resting CD8+ TRM after cleared infection with attenuated lymphocytic choriomeningitis virus (LCMV) can initiate responses...
The strength of T cell receptor (TCR) stimulation and asymmetric distribution fate determinants are both implied to affect differentiation. Here, we uncover division (ACD) as a safeguard mechanism for memory CD8 generation specifically upon strong TCR stimulation. Using live imaging approaches, find that induces elevated ACD rates, subsequent single-cell-derived colonies comprise effector precursor cells. abundance cells emerging from single activated positively correlates with first mitosis...
Although new genomics-based pipelines have potential to augment antibody discovery, these methods remain in their infancy due an incomplete understanding of the selection process that governs B cell clonal selection, expansion, and antigen specificity. Furthermore, it remains unknown how factors such as aging reduction tolerance influence selection. Here we perform single-cell sequencing repertoires transcriptomes murine cells following immunizations with a model therapeutic target. We...
Abstract Adaptive immune repertoires are composed by the ensemble of B and T-cell receptors within an individual, reflecting both past current responses. Recent advances in single-cell sequencing enable recovery complete adaptive receptor sequences addition to transcriptional information. Here, we recovered transcriptome repertoire information for polyclonal T follicular helper cells following lymphocytic choriomeningitis virus (LCMV) infection, CD8+ with binding specificity restricted two...
CD8+ T cells play a crucial role in the control and resolution of viral infections can adopt wide range phenotypes effector functions depending on inflammatory context duration extent antigen exposure. Similarly, exert diverse selective pressures populations clonally related cells. Technical limitations have nevertheless made it challenging to investigate relationship between clonal selection transcriptional virus-specific We therefore performed single-cell cell receptor (TCR) repertoire...
Abstract Plasma cells and their secreted antibodies play a central role in the long‐term protection against chronic viral infection. However, due to experimental limitations, comprehensive description of linked genotypic, phenotypic, antibody repertoire features plasma (gene expression, clonal frequency, virus specificity, affinity) has been challenging obtain. To address this, we performed single‐cell transcriptome sequencing murine BM cell population following lymphocytic choriomeningitis...
Abstract B cells contribute to the pathogenesis of both cellular- and humoral-mediated central nervous system (CNS) inflammatory diseases through a variety mechanisms. In such conditions, may enter CNS parenchyma local tissue destruction. It remains unexplored, however, how infection autoimmunity drive transcriptional phenotypes, repertoire features, antibody functionality. Here, we profiled from murine models intracranial (i.c.) viral infections autoimmunity. We identified population...
Abstract Motivation The maturation of systems immunology methodologies requires novel and transparent computational frameworks capable integrating diverse data modalities in a reproducible manner. Results Here, we present the ePlatypus ecosystem for immunogenomics analysis, with focus on adaptive immune repertoires single-cell sequencing. is an open-source web-based platform provides programming tutorials integrative database that helps elucidate signatures B T cell clonal selection....
Single-cell sequencing now enables the recovery of full-length immune receptor repertoires [B cell (BCR) and T (TCR) repertoires], in addition to gene expression information. The feature-rich datasets produced from such experiments require extensive diverse computational analyses, each which can significantly influence downstream immunological interpretations, as clonal selection expansion. Simulations produce validated standard datasets, where underlying generative model be precisely...
Abstract Adaptive immune repertoires are composed by the ensemble of B and T cell receptors (BCR, TCR) within an individual reflect both past current responses. Recent advances in single-cell sequencing enable recovery complete adaptive receptor sequences addition to transcriptional information. Such high-dimensional datasets molecular quantification clonal selection cells across a wide variety conditions such as infection disease. Due costs, time required for analysis practices academic...
Abstract Infection with influenza virus remains a significant global health concern due to its ability acquire mutations at key antigenic sites escape antibody recognition. While germinal center (GC) and memory B cells have been well studied following infection, the clonal dynamics of secreting (ASCs), particularly those within bone marrow (BM) niche that are responsible for serum immune protection, remain poorly understood. Here, we combine single-cell RNA (scRNA) cell receptor (BCR)...
Abstract Single-cell sequencing now enables the recovery of full-length immune repertoires [B cell receptor (BCR) and T (TCR) repertoires], in addition to gene expression information. The feature-rich datasets produced from such experiments require extensive diverse computational analyses, each which can significantly influence downstream immunological interpretations, as clonal selection expansion. Simulations produce validated standard datasets, where underlying generative model be...
Abstract The strength of T cell receptor (TCR) stimulation and asymmetric distribution fate determinants are both implied to affect differentiation. Here, we uncovered division (ACD) as a safeguard mechanism for memory CD8 generation specifically upon strong TCR stimulation. Using live imaging approaches, found that induced elevated ACD rates subsequent single derived colonies comprised effector precursor cells. abundance cells emerging from activated positively correlated with first mitosis...
Abstract B cells contribute to the pathogenesis of both cellular- and humoral-mediated central nervous system (CNS) inflammatory diseases through a variety mechanisms. In such conditions, may enter CNS parenchyma local tissue destruction. It remains unexplored, however, how infection autoimmunity drive transcriptional phenotypes, repertoire features, antibody functionality. Here, we profiled from murine models intracranial (i.c.) viral infections autoimmunity. We identified population...
Abstract The maturation of systems immunology methodologies requires novel and transparent computational frameworks capable integrating diverse data modalities in a reproducible manner. Here, we present the ePlatypus ecosystem for immunogenomics analysis, with focus on adaptive immune repertoires single-cell sequencing. is web-based platform provides programming tutorials an integrative database that elucidates selection patterns immunity. Furthermore, links established bioinformatics...