A5066382117- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Axon Guidance and Neuronal Signaling
- RNA Interference and Gene Delivery
- Adenosine and Purinergic Signaling
- HIV Research and Treatment
- Angiogenesis and VEGF in Cancer
- Mycorrhizal Fungi and Plant Interactions
- Legume Nitrogen Fixing Symbiosis
- Biomarkers in Disease Mechanisms
- Heat shock proteins research
- Immune Response and Inflammation
- Plant Parasitism and Resistance
- Erythrocyte Function and Pathophysiology
- Hippo pathway signaling and YAP/TAZ
- Blood properties and coagulation
MRC Human Immunology Unit
2019-2024
MRC Weatherall Institute of Molecular Medicine
2019-2024
University of Oxford
2016-2024
Oregon Health & Science University
2019-2024
Institute of Molecular Medicine
2021
VA Portland Health Care System
2020
University of Cambridge
2017
Medawar Building for Pathogen Research
2016
Constructor University
2015
Abstract Mucosal-associated invariant T (MAIT) cells are abundant in humans and recognize bacterial ligands. Here, we demonstrate that MAIT also activated during human viral infections vivo . activation was observed infection with dengue virus, hepatitis C virus influenza virus. This activation—driving cytokine release Granzyme B upregulation—is TCR-independent but dependent on IL-18 synergy IL-12, IL-15 and/or interferon-α/β. levels cell correlate disease severity acute infection....
The antigen-presenting molecule MR1 presents riboflavin-based metabolites to Mucosal-Associated Invariant T (MAIT) cells. While egress the cell surface is ligand-dependent, ability of small-molecule ligands impact on cellular trafficking remains unknown. Arising from an in silico screen ligand-binding pocket, we identify one ligand, 3-([2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl]formamido)propanoic acid, DB28, as well analog, methyl...
Abstract MR1-restricted T cells have been implicated in microbial infections, sterile inflammation, wound healing and cancer. Similar to other antigen presentation molecules, evidence supports multiple, complementary MR1 pathways. To investigate ligand exchange pathways for MR1, we used monomers tetramers loaded with 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil (5-OP-RU) deliver the antigen. Using MR1-deficient reconstituted wild-type or molecules that cannot bind 5-OP-RU, show of...
Abstract Semaphorin-3A (SEMA3A) functions as a chemorepulsive signal during development and can affect T cells by altering their filamentous actin (F-actin) cytoskeleton. The exact extent of these effects on tumour-specific are not completely understood. Here we demonstrate that Neuropilin-1 (NRP1) Plexin-A1 Plexin-A4 upregulated stimulated CD8 + cells, allowing tumour-derived SEMA3A to inhibit cell migration assembly the immunological synapse. Deletion NRP1 in both CD4 enhance T-cell...
Major histocompatibility complex class I proteins, which present antigenic peptides to cytotoxic T lymphocytes at the surface of all nucleated cells, are endocytosed and destroyed rapidly once their peptide ligand has dissociated. The molecular mechanism this cellular quality control process, prevents rebinding exogenous thus erroneous immune responses, is unknown. To identify nature decisive step in endocytic sorting molecules its location, we have followed removal optimally suboptimally...
In response to microbial infection, the nonclassical Ag-presenting molecule MHC class I-related protein 1 (MR1) presents secondary metabolites mucosal-associated invariant T (MAIT) cells. this study, we further characterize repertoire of ligands captured by MR1 produced in Hi5 (Trichoplusia ni) cells from Mycobacterium smegmatis via mass spectrometry. We describe (to our knowledge) novel ligand photolumazine (PL)V, a hydroxyindolyl-ribityllumazine with four isomers differing positioning...
ABSTRACT Semaphorin-3A (Sema3A) regulates tumor angiogenesis, but its role in modulating anti-tumor immunity is unclear. We demonstrate that Sema3A secreted within the microenvironment (TME) suppresses tumor-specific CD8+ T cell function via Neuropilin-1 (NRP1), a receptor upregulated upon activation with cells’ cognate antigen. inhibits migration, assembly of immunological synapse, and killing. It achieves these functional effects through hyper-activating acto-myosin system cells leading to...
Abstract MR1-restricted T cells have been implicated in microbial infections, sterile inflammation, wound healing and cancer. Similar to other antigen presentation molecules, evidence supports multiple, complementary MR1 pathways. To investigate ligand exchange pathways for MR1, we used monomers tetramers loaded with 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil (5-OP-RU) deliver the antigen. Using MR1-deficient reconstituted wild-type or molecules that cannot bind 5-OP-RU, show of...
Abstract The monomorphic antigen presenting molecule MHC-I-related protein 1 (MR1) presents small metabolites to mucosal-associated invariant T (MAIT) cells. MR1-MAIT cell axis has been implicated in a variety of infectious and non-communicable diseases recent studies have begun develop an understanding the molecular mechanisms underlying this specialised presentation pathway. Yet, proteins regulating MR1 folding, loading, stability, surface expression remain be identified. Here, we...