A5008376558- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- HIV Research and Treatment
- Monoclonal and Polyclonal Antibodies Research
- vaccines and immunoinformatics approaches
- Diabetes and associated disorders
- Head and Neck Cancer Studies
- Cancer Immunotherapy and Biomarkers
- Influenza Virus Research Studies
- Cytomegalovirus and herpesvirus research
- Immunodeficiency and Autoimmune Disorders
- Lymphoma Diagnosis and Treatment
- Epigenetics and DNA Methylation
- Trace Elements in Health
- Pancreatic function and diabetes
- Lung Cancer Research Studies
- Cervical Cancer and HPV Research
- T-cell and Retrovirus Studies
- Cancer Genomics and Diagnostics
- Ubiquitin and proteasome pathways
- Plant Micronutrient Interactions and Effects
- Aluminum toxicity and tolerance in plants and animals
- Diabetes Management and Research
Cardiff University
2016-2025
Kumamoto University
2025
University Hospital of Wales
2007-2021
Institute of Infection and Immunity
2017-2020
Yale University
2013-2017
Howard Hughes Medical Institute
2010
University of Colorado Boulder
2010
Medawar Building for Pathogen Research
2002-2008
University of Oxford
1999-2008
John Radcliffe Hospital
1997-2007
Cytotoxic T lymphocytes (CTLs) are thought to play a crucial role in the termination of acute primary HIV-1 syndrome, but clear evidence for this presumption has been lacking. Here we demonstrate positive selection proviral sequences encoding variants within CTL epitope Nef, gene product critical viral pathogenicity, during and after seroconversion. These positively selected carried sequence changes that either diminished or escaped recognition. Other proviruses had mutations abolished Nef...
The ability to decode antigen specificities encapsulated in the sequences of rearranged T-cell receptor (TCR) genes is critical for our understanding adaptive immune system and promises significant advances field translational medicine. Recent developments high-throughput sequencing methods (immune repertoire technology, or RepSeq) single-cell RNA technology have allowed us obtain huge numbers TCR from donor samples link them phenotypes. However, annotate these still lags behind, owing...
The T cell receptor (TCR) orchestrates immune responses by binding to foreign peptides presented at the surface in context of major histocompatibility complex (MHC) molecules. Effective immunity requires that all possible peptide-MHC molecules are recognized or risks leaving holes coverage pathogens could quickly evolve exploit. It is unclear how a limited pool <108 human TCRs can successfully provide vast array different be produced from 20 proteogenic amino acids and self-MHC (>1015...
The forces that govern clonal selection during the genesis and maintenance of specific T cell responses are complex, but amenable to decryption by interrogation constituent clonotypes within antigen-experienced pools. Here, we used point-mutated peptide–major histocompatibility complex class I (pMHCI) antigens, unbiased TCRB gene usage analysis, polychromatic flow cytometry probe directly ex vivo architecture antigen-specific CD8+ populations under conditions persistent exposure structurally...
The final pathway of β cell destruction leading to insulin deficiency, hyperglycemia, and clinical type 1 diabetes is unknown. Here we show that circulating CTLs can kill cells via recognition a glucose-regulated epitope. First, identified 2 naturally processed epitopes from the human preproinsulin signal peptide by elution HLA-A2 (specifically, protein encoded A*0201 allele) molecules. Processing these was unconventional, requiring neither proteasome nor transporter associated with...
Abstract Here, we report an update of the VDJdb database with a substantial increase in number T-cell receptor (TCR) sequences and their cognate antigens. The further provides new infrastructure featuring two additional analysis modes that facilitate querying real-world data analysis. increased yield TCR specificity identification methods overall studies field has allowed us to expand more than 5-fold. Furthermore, several are included. For example, batch annotation repertoire sequencing...
Antigen recognition by the T-cell receptor (TCR) is a hallmark of adaptive immune system. When TCR engages peptide bound to restricting major histocompatibility complex molecule (pMHC), it transmits signal via associated CD3 complex. How extracellular antigen event leads intracellular phosphorylation remains unclear. Here, we used single-molecule localization microscopy quantify organization TCR-CD3 complexes into nanoscale clusters and distinguish between triggered nontriggered complexes....
We studied the prevalent cytotoxic CD8 T cell response mounted against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike glycoprotein
The T cells of the immune system can target tumors and clear solid cancers following tumor-infiltrating lymphocyte (TIL) therapy. We used combinatorial peptide libraries a proteomic database to reveal antigen specificities persistent cancer-specific cell receptors (TCRs) successful TIL therapy for stage IV malignant melanoma. Remarkably, individual TCRs could multiple different tumor types via HLA A∗02:01-restricted epitopes EAAGIGILTV, LLLGIGILVL, NLSALGIFST from Melan A, BST2, IMP2,...
The T cell antigen presentation platform MR1 consists of 6 allomorphs in humans that differ by no more than 5 amino acids. principal function this highly conserved molecule involves presenting microbial metabolites to the abundant mucosal-associated invariant (MAIT) subset. Recent developments suggest role extends antigens from cancer cells, a dependent on K43 residue binding cleft. Here, we successfully cultured cancer-activated, MR1-restricted cells multiple donors and confirmed they...
Highly active antiretroviral therapy (HAART) has been advocated for the management of primary HIV-1 infection without clear understanding its immunological effects. Here, we demonstrate that early use HAART during preserves HIV-specific CD8(+) T cells physically and functionally while cell help is sustained. We also show even transient administration at seroconversion can preserve immunity. In contrast, delayed initiation associated with a progressive loss absent help. These results imply...
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...
Human immunodeficiency virus (HIV)-1 amino acid sequence polymorphisms associated with expression of specific human histocompatibility leukocyte antigen (HLA) class I alleles suggest sites cytotoxic T lymphocyte (CTL)-mediated selection pressure and immune escape. The associations most frequently observed are between an HLA molecule variation from the consensus sequence. However, a substantial number have been identified in which particular allele is preservation mechanism behind this so far...
Summary The bisphosphonates are a novel class of drug that have been registered for various clinical applications worldwide. Bisphosphonates, and in particular the aminobisphosphonates (nBPs), known to number side-effects including rise body temperature accompanying flu-like symptoms resemble typical acute phase response. mechanism this response has partially elucidated appears be associated with release tumour necrosis factor (TNF)α interleukin (IL)6, although effector cells these cytokines...
T cells have evolved a unique system of ligand recognition involving an antigen cell receptor (TCR) and coreceptor that integrate stimuli provided by the engagement peptide-major histocompatibility complex (pMHC) antigens. Here, we use altered pMHC class I (pMHCI) molecules with impaired CD8 binding (CD8-null) to quantify contribution extracellular (i) soluble tetrameric pMHCI molecules, (ii) kinetics TCR/pMHCI interactions on live cytotoxic lymphocytes (CTLs), (iii) activation CTLs...
Abstract T cell recognition is initiated by the binding of TCRs to peptide-MHCs (pMHCs), interaction being characterized weak affinity and fast kinetics. Previously, only 16 natural TCR/pMHC interactions have been measured surface plasmon resonance (SPR). Of these, 5 are murine class I, II, 6 human I-restricted responses. Therefore, a significant gap exists in our understanding due limited SPR data currently available for I responses absence II-restricted We produced panel soluble TCR...
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....
Primary human immunodeficiency virus (HIV) infection is controlled principally by HIV-specific cytotoxic T lymphocytes (CTL) to a steady-state level of load, which strongly influences the ultimate rate progression disease. Epitope selection CTL may be an important determinant degree immune control over virus. This report describes responses two HLA-identical hemophiliac brothers who were exposed identical batches Factor VIII and became seropositive within 10 wk one another. Both have...