A5091150350- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Immune Response and Inflammation
- Single-cell and spatial transcriptomics
- Invertebrate Immune Response Mechanisms
- Peptidase Inhibition and Analysis
- IL-33, ST2, and ILC Pathways
- Cell Adhesion Molecules Research
- Cancer Immunotherapy and Biomarkers
- Adenosine and Purinergic Signaling
- Xenotransplantation and immune response
- Calcium signaling and nucleotide metabolism
- interferon and immune responses
- Plant Virus Research Studies
- Malaria Research and Control
- Glycosylation and Glycoproteins Research
Medizinische Hochschule Hannover
2020-2024
University of Würzburg
2015-2020
Accumulating evidence suggests that the mouse embryonic thymus produces distinct waves of innate effector γδ T cells. However, it is unclear whether this process occurs similarly in humans and comprises a dedicated subset innate-like type 3 Here, we present protocol for high-throughput sequencing TRG TRD pairs comprise clonal γδTCR. In combination with single-cell RNA sequencing, multiparameter flow cytometry, TCR reveal high heterogeneity cells sorted from neonatal adult blood correlated...
Significance T cell receptors (TCRs) on the surface of cells mediate recognition antigen. Since each new carries an individual clonal TCR, monitoring TCR repertoires reflects how react and proliferate in response to environmental cues developing immune system neonates children. γδ appear early during ontogeny are important for surveillance. Here, we longitudinally analyze show immediate polyclonal expansion phosphoantigen-reactive Vγ9Vδ2 + after birth. We also observed differences children...
Preterm infants are at high risk of developing neonatal sepsis. γδ T cells thought to be an important set effector in neonates. Here, were investigated a longitudinal cohort preterm neonates using next-generation sequencing, flow cytometry, and functional assays. During the first year life, Vγ9Vδ2 cell subset showed dynamic phenotypic changes elevated levels fetal-derived evident with Single-cell transcriptomics identified HLA-DRhiCD83+ sepsis, which expressed genes related antigen...
Significance Human Vγ9Vδ2 T cells are important mediators of immunosurveillance and targets for cell-based immunotherapy. Activation by small molecular compounds called phosphoantigens is essential their functions involvement butyrophilins (BTN3A) has been shown. However, it not completely understood how the intracellular recognition BTN3 translated to cell surface finally activation. In addition, phosphoantigen-reactive were only identified in primates but rodents. this study, we present a...
Abstract Using full spectrum flow cytometry, we designed a 28‐color panel for the analysis of markers known to be associated with γδ T cell immune response. This allows classification subsets via specific V gene usage (Vγ9, Vδ1, Vδ2, and Vδ3) their receptor (TCR) according functional differentiation. Phenotypical surface receptors distinguish different stages maturation included CD45RA, CD27, CD28, CD127, CD57, CD16; chemokine CXCR6, CCR5, CCR6, CX3CR1; NK‐associated NKG2A, NKG2D, CD56,...
Abstract The Vγ9Vδ2 T cell subset is the major γδ in human peripheral blood and has unique ability to contribute immune surveillance by detecting pyrophosphorylated metabolites of isoprenoid synthesis, termed phosphoantigens (pAgs). cells are first detected at midgestation show postnatal expansion. Interestingly, neonatal display a higher TCR repertoire diversity with more public clonotypes lower pAg responsiveness than adults. Notably, it not known whether changes occur TCR-dependent...
Effector capabilities of γδ T cells are evident in Plasmodium infection young and adult individuals, while children the most vulnerable groups affected by malaria. Here, we aimed to investigate age-dependent phenotypic composition Vδ1 + , Vδ2 Vδ3 living endemic malaria areas how this differs between that will develop symptomatic asymptomatic falciparum infections. Flow cytometric profiling naïve effector peripheral blood was performed 6 neonates, 10 adults, 52 children. The study population...
(279 words) 1-5% of human blood T cells are Vγ9Vδ2 whose TCR contain a TRGV9/TRGJP rearrangement and TRDV2 comprising Vδ2-chain. They respond to phosphoantigens like isopentenyl pyrophosphate (IPP) or (E)-4-Hydroxy-3-methyl-but-2-enyl-pyrophosphate (HMBPP) in butyrophilin 3 (BTN3)-dependent manner may contribute the control mycobacterial infections. These were thought be restricted primates, but we demonstrated by analysis genomic databases that TRGV9, TRDV2, BTN3 genes coevolved emerged...
The clonal selection theory describes key features of adaptive immune responses B and T cells. For αβ cells cells, antigen recognition principles are known at a detailed molecular level. precise role the receptor in γδ remains less well understood. To better understand cell (TCR), we generate an orthotopic TCRδ transgenic mouse model. We demonstrate multi-layered functionality TCRs diverse roles CDR3δ-mediated during development. Whereas epithelial populations using Vγ5 or Vγ7 chains almost...
TCRs of invariant NKT (iNKT) cells bind α‐galactosylceramide (αGC) loaded CD1d in a highly conserved fashion and show characteristic TCR gene usage: An “invariant” α chain with canonical AV14 / AJ18 rearrangement mice ( AV24 humans) is paired β chains containing Vβ segments. In the rat, multimember family increases variability within this system. This study characterizes binding rat segments transductants as well iNKT expression expanded polyclonal F344 populations. It defines an important...
The cotton rat (Sigmodon hispidus) belongs to the rodent family of Cricetidae and provides a powerful model study pathogenesis human respiratory viruses measles virus. Recent studies in other models have suggested role for invariant natural killer T (iNKT) cells antiviral immunity vaccination against virus infections. Using new experimental tools, we provide first evidence functional CD1d cell molecule (crCD1d) iNKT T-cell receptor rats. crCD1d cDNA sequence was identified transductants...
Abstract Accumulating evidence suggests that the human embryonic thymus produces distinct waves of innate effector γδ T cells. However, it is unclear whether this process comprises a dedicated subset IL-17-producing (γδT17) cells, like reported in mice. Here we present novel protocol for high-throughput paired TCR-sequencing, which combination with single-cell RNA-sequencing revealed high heterogeneity cell clusters. While immature clusters displayed mixed and diverse TCR, types neonatal...
CD1d molecules are MHC class I-like that present glycolipids to iNKT cells. The highly conserved interaction between CD1d:α-Galactosylceramide (αGC) complexes and the TCR not only defines this population of αβ T cells but can also be used for its direct identification. Therefore, oligomers a widely tool cell related investigations. To end, lipid chains antigen have inserted into hydrophobic pockets binding cleft, often with help surfactants. In study, we investigated influence different...
In this thesis, three species were investigated for the conservation of two non-conventional T cell systems, CD1d/ iNKT system and BTN3/ Vγ9Vδ2 system. Non-conventional cells are αβ or γδ that do not fit into classical mode antigen recognition adaptive responses. These recognize antigens different from peptide restricted to polymorphic MHC molecules but rather non-polymorphic antigen-presenting molecules. The subset is by lipid molecule CD1d carries out immunomodulatory functions rapid...