A5031584855- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Celiac Disease Research and Management
- Monoclonal and Polyclonal Antibodies Research
- Lymphoma Diagnosis and Treatment
- Receptor Mechanisms and Signaling
- Lipid Membrane Structure and Behavior
- Cytomegalovirus and herpesvirus research
- Galectins and Cancer Biology
- Cell Adhesion Molecules Research
- Microfluidic and Bio-sensing Technologies
- Protein Kinase Regulation and GTPase Signaling
- Healthcare and Venom Research
- Heat shock proteins research
- Cancer Immunotherapy and Biomarkers
- Yersinia bacterium, plague, ectoparasites research
- Electrostatics and Colloid Interactions
- Transgenic Plants and Applications
- Microscopic Colitis
- Polymer Surface Interaction Studies
- Neuroscience and Neuropharmacology Research
- Protease and Inhibitor Mechanisms
Stanford University
2011-2019
Stanford Medicine
2012-2014
Palo Alto University
2011
Institute of Immunology
2010
University of Illinois Urbana-Champaign
2007
Materials Science & Engineering
2007
Abstract The β 2 adrenergic receptor (β AR) signals through both G s and i in cardiac myocytes, the pathway counteracts pathway. However, coupling is much less efficient than most cell-based biochemical assays, making it difficult to study AR−G interactions. Here we investigate role of phospholipid composition on coupling. While negatively charged phospholipids are known enhance agonist affinity stabilize an active state AR, find that they impair i3 facilitate . Positively Ca 2+ Mg ,...
The aim for deterministic control of the interactions between macroions in aqueous media has motivated widespread experimental and theoretical work. Although it been well established that like-charged macromolecules can aggregate under influence oppositely charged condensing agents, specific conditions stability such aggregates only be determined empirically. We examine these conditions, which involve an interplay electrostatic osmotic effects, by using a defined model system composed...
Abstract HLA-DM (DM) catalyzes CLIP release, stabilizes MHC class II molecules, and edits the peptide repertoire presented by II. Impaired DM function may have profound effects on Ag presentation events in thymus periphery that are critical for maintenance of self-tolerance. The associations HLA-DQ2 (DQ2) allele with celiac disease type 1 diabetes mellitus been appreciated a long time. explanation these associations, however, remains unknown. We previously found DQ2 is poor substrate DM. In...
For 15 y, α B-crystallin (heat shock protein [Hsp] B5) has been labeled an autoantigen in multiple sclerosis (MS) based on humoral and cellular responses found humans animal models. However, there have several scientific inconsistencies with this assignment, ranging from studies demonstrating small differences anticrystallin between patients healthy individuals to the inability of crystallin-specific T cells induce symptoms experimental allergic encephalomyelitis Experiments article...
Abstract The peptide-exchange catalyst, HLA-DM and its inhibitor, HLA-DO control endosomal generation of peptide/class II major histocompatibility protein (MHC-II) complexes; these complexes traffic to the cell surface for inspection by CD4+ T cells. Some evidence suggests that pH influences DO regulation DM function, but also affects stability polymorphic MHC-II proteins, spontaneous peptide loading, DM/MHC-II interactions catalytic activity, imposing challenges on approaches determine...
B cells internalize extracellular Ag into endosomes using the Ig component of BCR. In endosomes, Ag-derived peptides are loaded onto MHC class II proteins. How these pathways intersect remains unclear. We find that HLA-DM (DM), a catalyst for peptide loading, coprecipitates with in lysates from human tonsillar and cell lines. The molecules Ig/DM complexes have mature glycans, colocalize endosomal markers intact cells. A larger fraction precipitates DM after BCR crosslinking, implying can...
Summary The expression of major histocompatibility complex class II (MHC II) molecules is post‐translationally regulated by endocytic protein turnover. Here, we identified the serine protease cathepsin G (CatG) as an MHC II‐degrading in vitro screening and examined its role turnover vivo . CatG, uniquely among proteases tested, initiated cleavage detergent‐solubilized native recombinant soluble molecules. CatG cleaved human leukocyte antigen (HLA)‐DR isolated from both HLA‐DM‐expressing...
Abstract B cells internalize extracellular antigen into endosomes using the immunoglobulin (Ig) component of cell receptor. In endosomes, antigen-derived peptides are loaded onto MHC class II proteins (MHC-II). How these pathways intersect remains unclear. We previously found that HLA-DM (DM), a catalyst for MHC-II peptide loading, co-precipitates with Ig in lysates from human lines. also detected DM/Ig complexes intact by proximity ligation assay. Here, we report co-localize endosomal...
Abstract Peptide processing and loading onto MHC-II in endosomes occurs across a wide pH range. We studied effects on DM/DO regulation of peptide vitro, using soluble, recombinant molecules, including stabilized mutant DO dimer (sDOAP11A) that inhibits DM normally. tested different DO:DM ratios at 4.6-7.2 during 4 HLA alleles. alone had no effect. inhibition was diminished lower ratios, implying stable association is required for Inhibition occurred the range, but reduced 4.6. Using narrower...
Abstract CD4+ T cells recognize MHC-II-peptides, whose generation is controlled by HLA-DM and its inhibitor, HLA-DO. Activation of DM-DO-expressing alters DO:DM in favor active DM, but the molecular mechanism(s) underlying this process are unclear. DM known to catalyze exchange MHC-II-associated invariant chain peptides (CLIP) for antigenic peptides. As expected, We identified positive correlation between total CLIP level DO:DM, confirmed sufficient inhibition high cells. Importantly,...
Abstract HLA-DM (DM) catalyzes CLIP release, stabilizes MHC class II molecules and edits the peptide repertoire presented by II. Impaired DM function may have profound effects on antigen presentation events in thymus periphery that are critical for maintenance of self-tolerance. The associations HLA-DQ2 (DQ2) with autoimmune diseases, like celiac disease, been appreciated a long time. explanation these associations, however, remains unknown. We previously found DQ2 is poor substrate DM....
Abstract Antigen presenting cells (APC) are key regulators of immunity. They involved in stimulating naïve and effector critical for orchestrating protective responses to infectious agents as well aberrant self-antigens. Among APC, B uniquely capable small amounts antigen, which they capture take up through surface immunoglobulin (Ig). The uptake antigen by is studied, so the loading peptides onto MHC II, but how these two pathways intersect less elucidated. We propose that HLA-DM a factor...
Abstract G protein coupled receptors (GPCRs) are transmembrane that signal through heterotrimeric proteins. Lipid modifications anchor proteins to the plasma membrane; however, little is known about effect of phospholipid composition on GPCR-G coupling. The β 2 adrenergic receptor (β AR) signals both s and i in cardiac myocytes where studies suggest signaling may be cardioprotective. However, coupling much less efficient than most cell-based biochemical assays, making it difficult study AR-G...