A5024345109- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Autoimmune and Inflammatory Disorders Research
- Immunotherapy and Immune Responses
- Cellular transport and secretion
- CAR-T cell therapy research
- Parvovirus B19 Infection Studies
- Cytomegalovirus and herpesvirus research
- Monoclonal and Polyclonal Antibodies Research
- Calcium signaling and nucleotide metabolism
- Immunodeficiency and Autoimmune Disorders
- Lysosomal Storage Disorders Research
- Acute Lymphoblastic Leukemia research
- RNA Interference and Gene Delivery
- Genetic and Kidney Cyst Diseases
- melanin and skin pigmentation
- Neurogenetic and Muscular Disorders Research
- RNA regulation and disease
- HIV Research and Treatment
- Phagocytosis and Immune Regulation
- Adolescent and Pediatric Healthcare
- T-cell and Retrovirus Studies
- Glycosylation and Glycoproteins Research
- Cell death mechanisms and regulation
- Herpesvirus Infections and Treatments
University of Cambridge
2015-2024
Bridge University
2024
National Institute for Health Research
2016-2023
Addenbrooke's Hospital
2007-2018
Ninewells Hospital
2009-2017
Association of Surgeons of Great Britain and Ireland
2013
Sir Robert McAlpine (United Kingdom)
1999-2012
Cardiff University
2010
Wellcome Trust
2010
University of Oxford
2000-2009
Cell contact is required for efficient transmission of human T cell leukemia virus– type 1 (HTLV-I) between cells and individuals, because naturally infected lymphocytes produce virtually no cell-free infectious HTLV-I particles. However, the mechanism cell-to-cell spread not understood. We show here that rapidly induces polarization cytoskeleton to cell-cell junction. core (Gag protein) complexes genome accumulate at junction are then transferred uninfected cell. Other lymphotropic viruses,...
Rab27a activity is affected in several mouse models of human disease including Griscelli (ashen mice) and Hermansky-Pudlak (gunmetal syndromes. A loss function mutation occurs the gene ashen (ash), whereas gunmetal (gm) dysfunction secondary to a α subunit Rab geranylgeranyl transferase, an enzyme required for prenylation activation Rabs. We show here that normally expressed cytotoxic T lymphocytes (CTLs), but absent homozygotes (ash/ash). Cytotoxicity secretion assays ash/ash CTLs are...
Cytotoxic T lymphocytes (CTLs) use polarized secretion to rapidly destroy virally infected and tumor cells. To understand the temporal relationships between key events leading secretion, we used high-resolution 4D imaging. CTLs approached targets with actin-rich projections at edge, creating an initially actin-enriched contact rearward-flowing actin. Within 1 min, cortical actin reduced across synapse, cell receptors (TCRs) clustered centrally form central supramolecular activation cluster...
Abstract Tumor-specific T cells are frequently exhausted by chronic antigenic stimulation. We here report on a human antigen-specific ex vivo model to explore new therapeutic options for cell immunotherapies. generated with this resemble tumor-infiltrating phenotypic and transcriptional level. Using targeted pooled CRISPR-Cas9 screen individual gene knockout validation experiments, we uncover sorting nexin-9 (SNX9) as mediator of exhaustion. Upon TCR/CD28 stimulation, deletion SNX9 in CD8...
Analogue peptides with enhanced binding affinity to major histocompatibility class (MHC) I molecules are currently being used in cancer patients elicit stronger T cell responses. However, it remains unclear as how alterations of anchor residues may affect receptor (TCR) recognition. We correlate functional, thermodynamic, and structural parameters TCR–peptide–MHC demonstrate the effect residue modifications human leukocyte antigens (HLA)–A2 tumor epitope NY–ESO-1157–165–SLLMWITQC on TCR The...
Abstract CD8 + cytotoxic T lymphocyte (CTL) clones begin to synthesize the lytic proteins granzyme A, B and perforin after stimulation with allogeneic target cells. The are stored in secretory granules which released cross‐linking of cell receptor (TcR) upon recognition. During granule biogenesis A protein synthesis can be detected between 2 10 days CTL. Although is over this period, majority synthesized secreted directly from TcR triggering degranulation also results new proteins, inhibited...
CD1d-restricted lymphocytes recognize a broad lipid range. However, how translate T cell receptor (TCR) recognition of lipids with similar group heads into distinct biological responses remains unclear. Using soluble invariant NKT (iNKT) TCR and newly engineered antibody specific for α-galactosylceramide (α-GalCer)–human CD1d (hCD1d) complexes, we measured the affinity binding iNKT to hCD1d molecules loaded panel α-GalCer analogues assessed rate dissociation from molecules. We extended this...
Abstract Tetrameric peptide-MHC class I complexes (“tetramers”) are proving invaluable as reagents for characterizing immune responses involving CTLs. However, because the TCR can exhibit a degree of promiscuity binding ligands, there is potential cross-reactivity. Recent reports showing that TCR/peptide-MHC interaction dramatically dependent upon temperature led us to investigate effects incubation on tetramer staining. We find tetramers rapidly stain CTLs with high intensity at 37°C....