A5000565081- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- vaccines and immunoinformatics approaches
- Monoclonal and Polyclonal Antibodies Research
- Immune Response and Inflammation
- Amino Acid Enzymes and Metabolism
- Immune cells in cancer
- HIV Research and Treatment
- RNA Interference and Gene Delivery
- Metabolism and Genetic Disorders
- Glycosylation and Glycoproteins Research
- Cancer Research and Treatments
- Ubiquitin and proteasome pathways
- Cytomegalovirus and herpesvirus research
- Diet and metabolism studies
- Influenza Virus Research Studies
- Toxin Mechanisms and Immunotoxins
- Virus-based gene therapy research
- Immunodeficiency and Autoimmune Disorders
- interferon and immune responses
- Transgenic Plants and Applications
- Hepatitis B Virus Studies
John Radcliffe Hospital
2010-2025
University of Oxford
2016-2025
MRC Human Immunology Unit
2015-2024
MRC Weatherall Institute of Molecular Medicine
2013-2024
Institute of Molecular Medicine
2007-2023
Medical Research Council
2013-2023
National Institute for Health Research
2016-2019
Academy of Medical Sciences
2019
Chinese Academy of Medical Sciences & Peking Union Medical College
2019
Zero to Three
2016
Rheumatoid arthritis (RA) is a prevalent systemic autoimmune disease, caused by combination of genetic and environmental factors. Animal models suggest role for intestinal bacteria in supporting the immune response required joint inflammation. Here we performed 16S sequencing on 114 stool samples from rheumatoid patients controls, shotgun subset 44 such samples. We identified presence Prevotella copri as strongly correlated with disease new-onset untreated (NORA) patients. Increases...
Although cytotoxic T lymphocytes (CTLs) are thought to be involved in the control of human immunodeficiency virus–type 1 (HIV-1) infection, it has not been possible demonstrate a direct relation between CTL activity and plasma RNA viral load. Human leukocyte antigen–peptide tetrameric complexes offer specific means directly quantitate circulating CTLs ex vivo. With use complexes, significant inverse correlation was observed HIV-specific frequency In contrast, no association detected...
The nonclassical major histocompatibility complex (MHC) class I molecule HLA-E inhibits natural killer (NK) cell–mediated lysis by interacting with CD94/NKG2A receptors. Surface expression of depends on binding conserved peptides derived from MHC molecules. same peptide is present in the leader sequence human cytomegalovirus (HCMV) glycoprotein UL40 (gpUL40). It shown that, independently transporter associated antigen processing, gpUL40 can up-regulate HLA-E, which protects targets NK cell...
In mouse, a subset of dendritic cells (DCs) known as CD8α+ DCs has emerged an important player in the regulation T cell responses and promising target vaccination strategies. However, translation into clinical protocols been hampered by failure to identify humans. Here, we characterize population human that expresses DNGR-1 (CLEC9A) high levels BDCA3 resembles mouse phenotype function. We describe presence such spleens humans humanized mice report on protocol generate them vitro. Like DCs,...
The transcription factor FOXP3 plays a key role in CD4(+)CD25(+) regulatory T cell function and represents specific marker for these cells. Despite its strong association with function, humans little is known about the frequency of cells that express protein nor distribution vivo. Here we report characterization seven anti-FOXP3 monoclonal antibodies enabling detection endogenous human by flow cytometry immunohistochemistry. Flow-cytometric analysis showed was expressed majority...
Characterization of cytolytic T lymphocyte (CTL) responses to tumor antigens has been impeded by a lack direct assays CTL activity. We have synthesized reagents (“tetramers”) that specifically stain CTLs recognizing melanoma antigens. Tetramer staining tumor-infiltrated lymph nodes ex vivo revealed high frequencies tumor-specific which were antigen-experienced surface phenotype. In vitro culture node cells with cytokines resulted in very large expansions dependent on the presence nodes....
Using fluorescent HLA-A*0201 tetramers containing the immunodominant Melan-A/MART-1 (Melan-A) tumor-associated antigen (Ag), we previously observed that metastatic lymph nodes of melanoma patients contain high numbers Ag-experienced Melan-A-specific cytolytic T lymphocytes (CTLs). In this paper, enumerated and characterized ex vivo cells in peripheral blood samples from both healthy individuals. High frequencies (>/=1 2,500 CD8(+) cells) were found 10 out 13 patients, and, surprisingly, 6...
Modification in the function of dendritic cells (DC), such as that achieved by microbial stimuli or T cell help, plays a critical role determining quality and size adaptive responses to Ag. NKT bearing an invariant TCR (iNKT cells) restricted nonpolymorphic CD1d molecules may constitute readily available source help for DC. We therefore examined i.v. injection soluble Ag presence absence iNKT stimulation with CD1d-binding glycolipid alpha-galactosylceramide (alpha-GalCer). Considerably...
Dendritic cells (DCs) are potent antigen-presenting that initiate protective T-cell immunity in mice. To study the immunogenicity of DCs humans, we injected 9 healthy subjects subcutaneously with a control injection autologous monocyte-derived, mature DCs, followed 4–6 weeks later by pulsed keyhole limpet hemocyanin (KLH), HLA-A*0201–positive restricted influenza matrix peptide (MP), and tetanus toxoid (TT). Four more received these antigens without DCs. Injection unpulsed or alone, failed...
Vitiligo is an autoimmune condition characterized by loss of epidermal melanocytes. Using tetrameric complexes human histocompatibility leukocyte antigen (HLA) class I to identify antigen-specific T cells ex vivo, we observed high frequencies circulating MelanA-specific, A*0201-restricted cytotoxic lymphocytes (A2–MelanA tetramer+ CTLs) in seven nine HLA-A*0201–positive individuals with vitiligo. Isolated A2–MelanA CTLs were able lyse A*0201-matched melanoma vitro and their frequency vivo...
Abstract Leukocyte activation can be negatively regulated by inhibitory receptors specific for MHC class I molecules. While one receptor, Ig-like transcript 2 (ILT2), is expressed all lymphoid and myelomonocytic cell types, other display a more selective tissue distribution. Here we characterize an termed ILT4, which selectively in monocytes, macrophages, dendritic cells (DCs), binds classical molecules the nonclassical HLA-G, transduces negative signals that inhibit early signaling events...
NY-ESO-1, a member of the cancer–testis family antigens, is expressed in subset broad range different human tumor types. Patients with advanced NY-ESO-1-expressing tumors frequently develop humoral immunity to and three HLA A2-restricted peptides were defined previously as targets for cytotoxic CD8 + T cells melanoma patient NY-ESO-1 antibody. The objectives present study ( i ) enzyme-linked immunospot (ELISPOT) tetramer assays measure cell responses ii determine frequency series HLA-A2...
T cell antigen receptor (TCR) and coreceptor ligation is thought to initiate signal transduction by inducing activation of the kinase Lck.Here we showed that catalytically active Lck was present in unstimulated naive cells thymocytes readily detectable these lymphoid organs.In up ∼40% total constitutively activated, part which also phosphorylated on C-terminal inhibitory site.Formation activated independent TCR coreceptors but required catalytic activity its maintenance relied monitoring...
Infection with influenza A virus (IAV) presents a substantial threat to public health worldwide, young, elderly, and immunodeficient individuals being particularly susceptible. Inflammatory responses play an important role in the fatal outcome of IAV infection, but mechanism remains unclear. We demonstrate here that absence invariant NKT (iNKT) cells mice during infection resulted expansion myeloid-derived suppressor (MDSCs), which suppressed IAV-specific immune through expression both...
During infection, CD8(+) T cells initially expand then contract, leaving a small memory pool providing long lasting immunity. While it has been described that cell formation becomes defective in old age, the cellular mechanism is largely unknown. Autophagy major lysosomal degradation pathway of bulk material, and levels are known to fall with age. In this study, we describe novel role for autophagy formation. Mice lacking gene Atg7 failed establish influenza MCMV infection. Interestingly,...