A5102730050- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Endoplasmic Reticulum Stress and Disease
- Monoclonal and Polyclonal Antibodies Research
- Manufacturing Process and Optimization
- Advanced machining processes and optimization
- Glycosylation and Glycoproteins Research
- Advanced Sensor and Energy Harvesting Materials
- Cellular transport and secretion
- Advanced Surface Polishing Techniques
- Soft Robotics and Applications
- Adhesion, Friction, and Surface Interactions
- Optical measurement and interference techniques
- Robot Manipulation and Learning
- Pharmacogenetics and Drug Metabolism
- Pancreatic function and diabetes
- Receptor Mechanisms and Signaling
- Textile materials and evaluations
- Protein Degradation and Inhibitors
- Sports Dynamics and Biomechanics
- Iterative Learning Control Systems
- Advanced Measurement and Metrology Techniques
- Invertebrate Immune Response Mechanisms
- RNA and protein synthesis mechanisms
Royal Hospital for Children
2013-2024
Discovery Institute
2015-2024
Sanford Burnham Prebys Medical Discovery Institute
2012-2024
Royal Hospital for Sick Children
2021
Loughborough University
2009-2018
Engineering and Physical Sciences Research Council
2011-2018
Massachusetts Institute of Technology
1994-2018
General Atomics (United States)
1996-2018
Los Alamos National Laboratory
2018
Indiana University Bloomington
2018
The central event in the cellular immune response to invading microorganisms is specific recognition of foreign peptides bound major histocompatibility complex (MHC) molecules by alphabeta T cell receptor (TCR). x-ray structure complete extracellular fragment a glycosylated TCR was determined at 2.5 angstroms, and its orientation class I MHC-peptide (pMHC) elucidated from crystals TCR-pMHC complex. resembles an antibody variable Valpha Vbeta domains but deviates constant Calpha domain...
Peptide-major histocompatibility complex protein complexes (pMHCs) on antigen-presenting cells (APCs) are central to T cell activation. Within minutes of peptide-specific interacting with APCs, pMHCs APCs formed clusters at the site contact. Thereafter, these were acquired by and internalized through receptor-mediated endocytosis. During this process, became sensitive lysis neighboring (fratricide). This form immunoregulation could explain "exhaustion" responses that is induced high viral...
Calnexin is a molecular chaperone that resides in the membrane of endoplasmic reticulum. Most proteins calnexin binds are N-glycosylated, and treatment cells with tunicamycin or inhibitors initial glucose trimming steps interferes binding. To test if lectin early oligosaccharide processing intermediates, recombinant soluble was created. Incubation mixture Glc0–3Man9GlcNAc2 oligosaccharides resulted specific binding Glc1Man9GlcNAc2 species. Furthermore, Glc1Man5–7GlcNAc2 bound relatively...
A COOH-terminal double lysine motif maintains type I transmembrane proteins in the ER. Proteins tagged with this motif, eg., CD8/E19 and CD4/E19, rapidly receive post-translational modifications characteristic of intermediate compartment partially colocalized to organelle. These also received Golgi but much more slowly. Lectin staining localized these modified ER indicating that is a retrieval signal. Differences subcellular distribution rate modification CD8 maintained by sequences derived...
In this paper, a purely data-driven modelling approach is presented for predicting and controlling the free bending angle response of typical soft pneumatic actuator (SPA), embedded with resistive flex sensor. An experimental setup was constructed to test SPA at different input pressure values orientations, while recording resulting feedback from sensor on-board A calibrated high speed camera captures image frames during actuation, which are then analysed using an processing program...
Assembled class I histocompatibility molecules, consisting of heavy chain, β 2 -microglobulin, and peptide ligand, are transported rapidly to the cell surface. In contrast, intracellular transport free chains or peptide-deficient chain-β -microglobulin heterodimers is impaired. A 90-kilodalton membrane-bound chaperone endoplasmic reticulum (ER), termed calnexin, associates quantitatively with newly synthesized chains, but functions calnexin in this interaction unknown. Class subunits were...
ABSTRACT We describe, for the first time, generation of a viral DNA chip simultaneous expression measurements nearly all known open reading frames (ORFs) in largest member herpesvirus family, human cytomegalovirus (HCMV). In this study, an HCMV was fabricated and used to characterize temporal class gene expression. The is composed microarrays prepared by robotic deposition oligonucleotides on glass ORFs genome. Viral monitored hybridization oligonucleotide with fluorescently labelled cDNAs...
CD1 molecules are distantly related to the major histocompatibility complex (MHC) class I proteins. They of unknown function. Screening random peptide phage display libraries with soluble empty mouse (mCD1) identified a binding motif. It consists three anchor positions occupied by aromatic or bulky hydrophobic amino acids. Equilibrium studies demonstrated that mCD1 binds peptides containing appropriate motif relatively high affinity. However, in contrast classical MHC molecules, strong...
At the site of contact between T cells and antigen-presenting (APCs), cell receptor (TCR)–peptide–major histocompatibility complex (MHC) interaction is intensified by interactions other molecules, notably CD28 lymphocyte function-associated antigen 1 (LFA-1) on interacting with B7 (B7-1 B7-2), intracellular adhesion molecule (ICAM-1), respectively, APCs. Here, we show that during cell–APC interaction, rapidly absorb various molecules from APCs onto membrane then internalize these molecules....
Recent reports have suggested that major histocompatibility complex class II molecules load peptide through a specialized compartment of the endocytic pathway and are targeted to this by association with invariant chain (Iip31). Therefore we used site-directed mutagenesis approach determine whether Iip31 possesses novel protein targeting signals. Our results indicate two di-leucine-like pairs mediate an acidic amino acid residue four or five residues N-terminal each pair is required for...
Human cytomegalovirus (HCMV) infection alters the expression of many cellular genes, including IFN-stimulated genes (ISGs) [Zhu, H., Cong, J.-P., Mamtora, G., Gingeras, T. & Shenk, (1998) Proc. Natl. Acad. Sci. USA 95, 14470–14475]. By using high-density cDNA microarrays, we show that HCMV-regulated gene profile in fibroblasts does not differ substantially from response generated by IFN. Furthermore, identified specific viral component triggering this as envelope glycoprotein B (gB)....
We report here that the intrinsic affinities of antigen-specific T-cell receptors (TCR) two unrelated CD8+ clones for their respective peptide-major histocompatibility complex (MHC) ligands are higher than values generally thought to prevail TCR. The TCR one clone (2C) binds an allogeneic class I MHC protein (Ld) in association with alpha-ketoglutarate dehydrogenase nonapeptide (QLSPFPFDL, termed QL9) affinity (intrinsic equilibrium constant) 1-2 x 10(7) M-1. other (4G3) a syngeneic (Kb)...
ABSTRACT Medial vascular calcification (MVC) is a pathological phenomenon that causes stiffening and can lead to heart failure; it common variety of conditions, including aging, chronic kidney disease, diabetes, obesity, rare genetic diseases. These conditions share the feature tissue-nonspecific alkaline phosphatase (TNAP) upregulation in vasculature. To evaluate role TNAP MVC, we developed mouse model overexpresses human smooth muscle cells an X-linked manner. Hemizygous overexpressor male...
The requirements for inducing downregulation of α/β T cell receptor (TCR) molecules on naive major histocompatibility complex class I–restricted cells was investigated with 2C TCR transgenic mice and defined peptides as antigen. Confirming previous results, activation in response to specific required CD8 expression the responder heavily dependent upon costimulation provided by either B7-1 or ICAM-1 antigen-presenting (APC). These stringent did not apply downregulation. Thus, seemed depend...
Hereditary hemochromatosis is a common autosomal recessive disorder of iron metabolism. Recent demonstration an association between transferrin receptor (TfR) and HFE, major histocompatibility complex class I-like molecule that has been implicated to play role in hereditary hemochromatosis, further strengthens the notion HFE involved Herein we show TfR required for controls assembly intracellular transport surface expression HFE. Because surface-expressed remain firmly associated physically,...
To assess the sensitivity of B cell tolerance with respect to receptor/autoantigen affinity, we identified low affinity ligands 3-83 (anti-major histocompatibility complex class I) antibody and tested ability these induce central peripheral in transgenic mice. Several I protein alloforms, including Kbm3 Dk, showed remarkably low, but detectable, 3-83. The bound Kb K lambda approximately 2 x 10(5) M-1 10-fold more weakly (K 10(4) M-1) Dk antigens. Breeding immunoglobulin mice expressing...