A5016792406- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Virus-based gene therapy research
- T-cell and B-cell Immunology
- CAR-T cell therapy research
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Monoclonal and Polyclonal Antibodies Research
- vaccines and immunoinformatics approaches
- Enzyme Structure and Function
- Glycosylation and Glycoproteins Research
- Protein Structure and Dynamics
- Click Chemistry and Applications
- Viral Infectious Diseases and Gene Expression in Insects
- Cancer Immunotherapy and Biomarkers
- Photosynthetic Processes and Mechanisms
- Advanced Fluorescence Microscopy Techniques
- Bacteriophages and microbial interactions
- Animal Virus Infections Studies
- Stochastic processes and statistical mechanics
- Calpain Protease Function and Regulation
- HIV Research and Treatment
- Magnetism in coordination complexes
- Theoretical and Computational Physics
- Photoreceptor and optogenetics research
Cardiff University
2015-2024
PHENIX laboratory
2023-2024
Sorbonne Université
2023-2024
Centre National de la Recherche Scientifique
2023-2024
Sorbonne University Abu Dhabi
2024
Institute of Infection and Immunity
2017-2020
University Hospital of Wales
2017-2019
Sapporo Medical University
2019
Indiana University School of Medicine
2015
Cardiff Metropolitan University
2014
We observe previously unknown interactions between clinically important adenovirus vector capsids, platelet factor 4, and CAR.
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,...
Antibody and T-cell receptors (TCRs) are the primary recognition molecules of adaptive immune system. Antibodies have been extensively characterized being developed for a large number therapeutic applications. This has possible because ability to manufacture stable, soluble, monoclonal antibodies which retain antigen specificity B cells. Unlike antibodies, TCRs not expressed in soluble form, but anchored surface by an insoluble trans-membrane domain. Characterization development hampered...
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...
The binding of the carotenoid astaxanthin (AXT) in protein multimacromolecular complex crustacyanin (CR) is responsible for blue coloration lobster shell. structural basis bathochromic shift mechanism has long been elusive. A change color occurs from orange red unbound dilute AXT (lambda(max) 472 nm hexane), well-known cooked lobster, to slate protein-bound live state 632 CR). Intriguingly, extracted CR becomes on dehydration and rehydration goes back blue. Recently, innovative use softer...
A tripodal cyclotriveratrylene-based ligand with chelating 2,2'-bipyridine arms self-assembles either Zn(NO3)2 or Co(NO3)2 to give 3-D trigonal bipyramidal [M3L2] cage assemblies. These cages triply interlock forming [2]catenane species that have been characterized by mass spectrometry and, in the case of Zn(II) complex, X-ray crystallography.
The metal–organic frameworks NOTT-400 and NOTT-401, based on a binuclear [Sc2(μ2-OH)(O2CR)4] building block, have been synthesised characterised; the desolvated framework NOTT-401a shows BET surface area of 1514 m2 g−1 with total H2 uptake 4.44 wt% at 77 K 20 bar.
CD8(+) T-cells specific for MART-1-(26-35), a dominant melanoma epitope restricted by human leukocyte antigen (HLA)-A*0201, are exceptionally common in the naive T-cell repertoire. Remarkably, TRAV12-2 gene is used to encode receptor alpha (TCRalpha) chain >87% of these T-cells. Here, molecular basis this genetic bias revealed from structural and thermodynamic properties an archetypal TRAV12-2-encoded TCR complexed clinically relevant heteroclitic peptide, ELAGIGILTV, bound HLA-A*0201...
Enhanced Green Fluorescent Protein (EGFP) is one of the most widely used engineered variants original wild-type Protein. Here, we report high resolution (1.35 Å) structure EGFP crystallised in its untagged sequence form that reveals combined impact F64L and S65T, give rise to improved folding spectral characteristics. The overall very similar wt GFP, forming classical β-barrel fold with chromophore containing helix running through core structure. Replacement Phe64 Leu results subtle...
The cross-reactivity of T cells with pathogen- and self-derived peptides has been implicated as a pathway involved in the development autoimmunity. However, mechanisms that allow clonal cell antigen receptor (TCR) to functionally engage multiple peptide–major histocompatibility complexes (pMHC) are unclear. Here, we studied multiligand discrimination by human, preproinsulin reactive, MHC class-I–restricted CD8+ clone (1E6) can recognize over 1 million different peptides. We generated...
Adenoviruses are clinically important agents. They cause respiratory distress, gastroenteritis, and epidemic keratoconjunctivitis. As non-enveloped, double-stranded DNA viruses, they easily manipulated, making them popular vectors for therapeutic applications, including vaccines. Species D adenovirus type 26 (HAdV-D26) is both a of EKC other diseases promising vaccine vector. HAdV-D26-derived vaccines under investigation as protective platforms against HIV, Zika, syncytial virus infections...
Tumor-associated peptide–human leukocyte antigen complexes (pHLAs) represent the largest pool of cell surface–expressed cancer-specific epitopes, making them attractive targets for cancer therapies. Soluble bispecific molecules that incorporate an anti-CD3 effector function are being developed to redirect T cells against these using 2 different approaches. The first achieves pHLA recognition via affinity-enhanced versions natural TCRs (e.g., immune-mobilizing monoclonal receptors [ImmTAC]...
Despite the ∼1018 αβ T cell receptor (TCR) structures that can be randomly manufactured by human thymus, some surface more frequently than others. The pinnacles of this distortion are public TCRs, which exhibit amino acid-identical across different individuals. Public TCRs thought to result from both recombinatorial bias and antigen-driven selection, but mechanisms underlie inter-individual TCR sharing still largely theoretical. To examine phenomenon at atomic level, we solved co-complex...
Abstract Natural T-cell responses generally lack the potency to eradicate cancer. Enhanced affinity receptors (TCRs) provide an ideal approach target cancer cells, with emerging clinical data showing significant promise. Nevertheless, risk of off reactivity remains a key concern, as exemplified in recent report describing fatal cardiac toxicity, following administration MAGE-A3 specific TCR-engineered T-cells, mediated through cross-reactivity unrelated epitope from Titin protein presented...
MHC anchor residue‐modified “heteroclitic” peptides have been used in many cancer vaccine trials and often induce greater immune responses than the wild‐type peptide. The best‐studied system to date is decamer MART‐1/Melan‐A 26–35 peptide, EAAGIGILTV, where natural alanine at position 2 has modified leucine improve human leukocyte antigen (HLA)‐A*0201 anchoring. resulting E L AGIGILTV peptide studies. We recently showed that T cells primed with can fail recognize tumor‐expressed efficiently,...
Adenovirus based vectors are of increasing importance for wide ranging therapeutic applications. As vaccines, derived from human adenovirus species D serotypes 26 and 48 (HAdV-D26/48) demonstrating promising efficacy as protective platforms against infectious diseases. Significant clinical progress has been made, yet definitive studies underpinning mechanisms entry, infection, receptor usage currently lacking. Here, we perform structural biological analysis the binding fiber-knob protein...
Absolute negative mobility (ANM) refers to the situation where average velocity of a driven tracer is opposite direction driving force. This effect was evidenced in different models nonequilibrium transport complex environments, whose description remains effective. Here, we provide microscopic theory for this phenomenon. We show that it emerges model an active particle submitted external force and which evolves on discrete lattice populated with mobile passive crowders. Resorting decoupling...