ORCID Profile
0000-0002-8457-6693
Current Organisation
La Jolla Institute for Allergy and Immunology
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Publisher: The American Association of Immunologists
Date: 15-07-2021
Abstract: Upon Ag encounter, T cells can rapidly ide and form an effector population, which plays an important role in fighting acute infections. In humans, little is known about the molecular markers that distinguish such effector cells from other T cell populations. To address this, we investigated the molecular profile of T cells present in in iduals with active tuberculosis (ATB), where we expect Ag encounter and expansion of effector cells to occur at higher frequency in contrast to Mycobacterium tuberculosis–sensitized healthy IGRA+ in iduals. We found that the frequency of HLA-DR+ cells was increased in circulating CD4 T cells of ATB patients, and was dominantly expressed in M. tuberculosis Ag–specific CD4 T cells. We tested and confirmed that HLA-DR is a marker of recently ided CD4 T cells upon M. tuberculosis Ag exposure using an in vitro model examining the response of resting memory T cells from healthy IGRA+ to Ags. Thus, HLA-DR marks a CD4 T cell population that can be directly detected ex vivo in human peripheral blood, whose frequency is increased during ATB disease and contains recently ided Ag-specific effector T cells. These findings will facilitate the monitoring and study of disease-specific effector T cell responses in the context of ATB and other infections.
Publisher: eLife Sciences Publications, Ltd
Date: 30-05-2019
Publisher: American Society for Clinical Investigation
Date: 18-03-2019
DOI: 10.1172/JCI123726
Publisher: The American Association of Immunologists
Date: 06-2020
DOI: 10.4049/IMMUNOHORIZONS.2000031
Abstract: CD8 T cells are considered important contributors to the immune response against Mycobacterium tuberculosis, yet limited information is currently known regarding their specific immune signature and phenotype. In this study, we applied a cell population transcriptomics strategy to define immune signatures of human latent tuberculosis infection (LTBI) in memory CD8 T cells. We found a 41-gene signature that discriminates between memory CD8 T cells from healthy LTBI subjects and uninfected controls. The gene signature was dominated by genes associated with mucosal-associated invariant T cells (MAITs) and reflected the lower frequency of MAITs observed in in iduals with LTBI. There was no evidence for a conventional CD8 T cell–specific signature between the two cohorts. We, therefore, investigated MAITs in more detail based on Vα7.2 and CD161 expression and staining with an MHC-related protein 1 (MR1) tetramer. This revealed two distinct populations of CD8+Vα7.2+CD161+ MAITs: MR1 tetramer+ and MR1 tetramer−, which both had distinct gene expression compared with memory CD8 T cells. Transcriptomic analysis of LTBI versus noninfected in iduals did not reveal significant differences for MR1 tetramer+ MAITs. However, gene expression of MR1 tetramer− MAITs showed large interin idual ersity and a tuberculosis-specific signature. This was further strengthened by a more erse TCR-α and -β repertoire of MR1 tetramer− cells as compared with MR1 tetramer+. Thus, circulating memory CD8 T cells in subjects with latent tuberculosis have a reduced number of conventional MR1 tetramer+ MAITs as well as a difference in phenotype in the rare population of MR1 tetramer− MAITs compared with uninfected controls.
Publisher: Cold Spring Harbor Laboratory
Date: 09-12-2020
DOI: 10.1101/2020.12.08.416750
Abstract: T cells are involved in control of SARS-CoV-2 infection. To establish the patterns of immunodominance of different SARS-CoV-2 antigens, and precisely measure virus-specific CD4 + and CD8 + T cells, we studied epitope-specific T cell responses of approximately 100 convalescent COVID-19 cases. The SARS-CoV-2 proteome was probed using 1,925 peptides spanning the entire genome, ensuring an unbiased coverage of HLA alleles for class II responses. For HLA class I, we studied an additional 5,600 predicted binding epitopes for 28 prominent HLA class I alleles, accounting for wide global coverage. We identified several hundred HLA-restricted SARS-CoV-2-derived epitopes. Distinct patterns of immunodominance were observed, which differed for CD4 + T cells, CD8 + T cells, and antibodies. The class I and class II epitopes were combined into new epitope megapools to facilitate identification and quantification of SARS-CoV-2-specific CD4 + and CD8 + T cells.
Publisher: The American Association of Immunologists
Date: 15-02-2017
Abstract: In the context of large-scale human system immunology studies, controlling for technical and biological variability is crucial to ensure that experimental data support research conclusions. In this study, we report on a universal workflow to evaluate both technical and biological variation in multiparameter flow cytometry, applied to the development of a 10-color panel to identify all major cell populations and T cell subsets in cryopreserved PBMC. Replicate runs from a control donation and comparison of different gating strategies assessed the technical variability associated with each cell population and permitted the calculation of a quality control score. Applying our panel to a large collection of PBMC s les, we found that most cell populations showed low intrain idual variability over time. In contrast, certain subpopulations such as CD56 T cells and Temra CD4 T cells were associated with high interin idual variability. Age but not gender had a significant effect on the frequency of several populations, with a drastic decrease in naive T cells observed in older donors. Ethnicity also influenced a significant proportion of immune cell population frequencies, emphasizing the need to account for these covariates in immune profiling studies. We also exemplify the usefulness of our workflow by identifying a novel cell-subset signature of latent tuberculosis infection. Thus, our study provides a universal workflow to establish and evaluate any flow cytometry panel in systems immunology studies.
Publisher: Elsevier BV
Date: 12-2021
Publisher: eLife Sciences Publications, Ltd
Date: 25-06-2019
DOI: 10.7554/ELIFE.46045
Abstract: Our results highlight for the first time that a significant proportion of cell doublets in flow cytometry, previously believed to be the result of technical artifacts and thus ignored in data acquisition and analysis, are the result of biological interaction between immune cells. In particular, we show that cell:cell doublets pairing a T cell and a monocyte can be directly isolated from human blood, and high resolution microscopy shows polarized distribution of LFA1/ICAM1 in many doublets, suggesting in vivo formation. Intriguingly, T cell-monocyte complex frequency and phenotype fluctuate with the onset of immune perturbations such as infection or immunization, reflecting expected polarization of immune responses. Overall these data suggest that cell doublets reflecting T cell-monocyte in vivo immune interactions can be detected in human blood and that the common approach in flow cytometry to avoid studying cell:cell complexes should be re-visited.
Publisher: Springer Science and Business Media LLC
Date: 16-11-2017
DOI: 10.1038/NI.3873
Publisher: The American Association of Immunologists
Date: 05-2018
Abstract: In the context of infectious diseases, cell population transcriptomics are useful to gain mechanistic insight into protective immune responses, which is not possible using traditional whole-blood approaches. In this study, we applied a cell population transcriptomics strategy to sorted memory CD4 T cells to define novel immune signatures of latent tuberculosis infection (LTBI) and gain insight into the phenotype of tuberculosis (TB)-specific CD4 T cells. We found a 74-gene signature that could discriminate between memory CD4 T cells from healthy latently Mycobacterium tuberculosis–infected subjects and noninfected controls. The gene signature presented a significant overlap with the gene signature of the Th1* (CCR6+CXCR3+CCR4−) subset of CD4 T cells, which contains the majority of TB-specific reactivity and is expanded in LTBI. In particular, three Th1* genes (ABCB1, c-KIT, and GPA33) were differentially expressed at the RNA and protein levels in memory CD4 T cells of LTBI subjects compared with controls. The 74-gene signature also highlighted novel phenotypic markers that further defined the CD4 T cell subset containing TB specificity. We found the majority of TB-specific epitope reactivity in the CD62L−GPA33− Th1* subset. Thus, by combining cell population transcriptomics and single-cell protein-profiling techniques, we identified a CD4 T cell immune signature of LTBI that provided novel insights into the phenotype of TB-specific CD4 T cells.
Publisher: The American Association of Immunologists
Date: 07-2019
Abstract: Tau protein is found to be aggregated and hyperphosphorylated (p-tau) in many neurologic disorders, including Parkinson disease (PD) and related parkinsonisms, Alzheimer disease, traumatic brain injury, and even in normal aging. Although not known to produce autoimmune responses, we hypothesized that the appearance of aggregated tau and p-tau with disease could activate the immune system. We thus compared T cell responses to tau and p-tau–derived peptides between PD patients, age-matched healthy controls, and young healthy controls (& y old who are less likely to have high levels of tau aggregates). All groups exhibited CD4+ T cell responses to tau-derived peptides, which were associated with secretion of IFN-γ, IL-5, and/or IL-4. The PD and control participants exhibited a similar magnitude and breadth of responses. Some tau-derived epitopes, consisting of both unmodified and p-tau residues, were more highly represented in PD participants. These results were verified in an independent set of PD and control donors (either age-matched or young controls). Thus, T cells recognizing tau epitopes escape central and peripheral tolerance in relatively high numbers, and the magnitude and nature of these responses are not modulated by age or PD disease.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 02-10-2020
Abstract: Robust T cell responses to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus occur in most in iduals with coronavirus disease 2019 (COVID-19). Several studies have reported that some people who have not been exposed to SARS-CoV-2 have preexisting reactivity to SARS-CoV-2 sequences. The immunological mechanisms underlying this preexisting reactivity are not clear, but previous exposure to widely circulating common cold coronaviruses might be involved. Mateus et al. found that the preexisting reactivity against SARS-CoV-2 comes from memory T cells and that cross-reactive T cells can specifically recognize a SARS-CoV-2 epitope as well as the homologous epitope from a common cold coronavirus. These findings underline the importance of determining the impacts of preexisting immune memory in COVID-19 disease severity. Science , this issue p. 89
Publisher: American Association for the Advancement of Science (AAAS)
Date: 05-02-2021
Abstract: Immune memory against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) helps to determine protection against reinfection, disease risk, and vaccine efficacy. Using 188 human cases across the range of severity of COVID-19, Dan et al. analyzed cross-sectional data describing the dynamics of SARS-CoV-2 memory B cells, CD8 + T cells, and CD4 + T cells for more than 6 months after infection. The authors found a high degree of heterogeneity in the magnitude of adaptive immune responses that persisted into the immune memory phase to the virus. However, immune memory in three immunological compartments remained measurable in greater than 90% of subjects for more than 5 months after infection. Despite the heterogeneity of immune responses, these results show that durable immunity against secondary COVID-19 disease is a possibility for most in iduals. Science , this issue p. eabf4063
Publisher: Oxford University Press (OUP)
Date: 2022
Abstract: Similar to managing software packages, managing the ontology life cycle involves multiple complex workflows such as preparing releases, continuous quality control checking and dependency management. To manage these processes, a erse set of tools is required, from command-line utilities to powerful ontology-engineering environmentsr. Particularly in the biomedical domain, which has developed a set of highly erse yet inter-dependent ontologies, standardizing release practices and metadata and establishing shared quality standards are crucial to enable interoperability. The Ontology Development Kit (ODK) provides a set of standardized, customizable and automatically executable workflows, and packages all required tooling in a single Docker image. In this paper, we provide an overview of how the ODK works, show how it is used in practice and describe how we envision it driving standardization efforts in our community. Database URL: github.com/INCATools/ontology-development-kit
Publisher: Public Library of Science (PLoS)
Date: 26-05-2020
Location: United States of America
No related grants have been discovered for Bjoern Peters.