A5032719628- Immune Cell Function and Interaction
- HIV Research and Treatment
- T-cell and B-cell Immunology
- Monoclonal and Polyclonal Antibodies Research
- Immunodeficiency and Autoimmune Disorders
- HIV/AIDS drug development and treatment
- Chronic Lymphocytic Leukemia Research
- Immune Response and Inflammation
- Natural Compounds in Disease Treatment
- HIV/AIDS Research and Interventions
- Systemic Lupus Erythematosus Research
- Renal Diseases and Glomerulopathies
- Glycosylation and Glycoproteins Research
- Diabetes and associated disorders
- Cell Adhesion Molecules Research
- Lymphoma Diagnosis and Treatment
- Psoriasis: Treatment and Pathogenesis
- HIV-related health complications and treatments
- bioluminescence and chemiluminescence research
- NF-κB Signaling Pathways
- Bacteriophages and microbial interactions
- Cell death mechanisms and regulation
- Food Allergy and Anaphylaxis Research
- Radioactive contamination and transfer
- Radiation Effects and Dosimetry
National Institutes of Health
2008-2017
National Institute of Allergy and Infectious Diseases
2010-2017
University of Pittsburgh Medical Center
2017
Novo Nordisk (Denmark)
2012
Beth Israel Deaconess Medical Center
2012
Harvard University
2012
University of Washington
2012
National Institute of Arthritis and Musculoskeletal and Skin Diseases
2001-2011
Analysis Group (United States)
2007
University of Maryland, College Park
2003
Cross-reactive neutralizing antibodies (NAbs) are found in the sera of many HIV-1-infected individuals, but virologic basis their neutralization remains poorly understood. We used knowledge HIV-1 envelope structure to develop antigenically resurfaced glycoproteins specific for structurally conserved site initial CD4 receptor binding. These probes were identify with NAbs CD4-binding (CD4bs) and isolate individual B cells from such an donor. By expressing immunoglobulin genes cells, we...
Broadly neutralizing antibodies to HIV with similar specificities can be found in multiple HIV-infected individuals.
We analyzed 77 nonproductive and 574 productive human V(H)DJ(H) rearrangements with a newly developed program, JOINSOLVER. In the repertoire, H chain complementarity determining region 3 (CDR3(H)) was significantly shorter (46.7 +/- 0.5 nucleotides) than in repertoire (53.8 1.9 because of tendency to select less TdT activity D segments. Using criteria established by Monte Carlo simulations, segments could be identified 71.4% 64.4% rearrangements, mean 17.6 0.7 14.6 0.2 retained germline...
Background Antibodies (Abs) produced during HIV-1 infection rarely neutralize a broad range of viral isolates; only eight broadly-neutralizing (bNt) monoclonal (M)Abs have been isolated. Yet, to be effective, an vaccine may elicit the essential features these MAbs. The V genes all bNt MAbs are highly somatically mutated, and VH five them encode long (≥20 aa) third complementarity-determining region (CDR-H3). This led us question whether CDR-H3s high levels somatic mutation (SM) preferred...
ABSTRACT The gp120 CD4 binding site (CD4bs) and coreceptor (CoRbs) are two functionally conserved elements of the HIV-1 envelope glycoproteins (Env). We previously defined presence CD4bs-neutralizing antibodies in serum an HIV-1-infected individual subsequently isolated CD4bs-specific monoclonal (MAbs) VRC01 VRC03 from memory B cell population. Since this donor's also appeared to contain neutralizing CoRbs, we employed a differential fluorescence-activated sorter (FACS)-based sorting...
Antibody 10E8 targets the membrane-proximal external region (MPER) of HIV-1 gp41, neutralizes >97% isolates, and lacks auto-reactivity often associated with MPER-directed antibodies. The developmental pathway might therefore serve as a promising template for vaccine design, but samples from time-of-infection-often used to infer B cell record-are unavailable. In this study, we crystallography, next-generation sequencing (NGS), functional assessments single time point. Mutational analysis...
One of the goals HIV-1 vaccine development is elicitation neutralizing antibodies against vulnerable regions on envelope glycoprotein (Env) viral spike. Broadly targeting Env glycan-V3 region (also called N332 glycan supersite) have been described previously, with several single lineages each derived from different individual donors. We used a high-throughput B-cell culture method to isolate an HIV-1-infected donor high serum neutralization breadth. Clonal relatives three distinct antibody...
Abstract Objective Triptolide and tripdiolide are thought to be active components of the Chinese antirheumatic herbal remedy Tripterygium wilfordii Hook F, which has been shown effective in treating murine lupus nephritis. This study was undertaken examine therapeutic effect triptolide on established nephritis (NZB × NZW)F 1 mice. Methods mice were treated with vehicle, triptolide, or for 15 weeks beginning at age 29 (after development nephritis). Body weight, proteinuria,...
This study was designed to examine the potential use of ethyl acetate (EA) extract Tripterygium wilfordii Hook F (TwHF), a Chinese herbal medicine, in treatment systemic lupus erythematosus. A total 48 28-week-old female NZB/W F1 mice were randomly divided into three groups and orally administered vehicle or EA TwHF at 18.25 mg/kg (EAlow) 36.5 (EAhigh) for 14 weeks. Proteinuria serum anti-double-stranded (ds)DNA antibody titers assayed before after treatment. At end treatment, all animals...
Abstract Protein A (SpA) of Staphylococcus aureus is endowed with the capacity to interact H chain variable region (VH) human Abs and target >40% B lymphocytes. To investigate whether this property represents a virulence factor determine in vivo consequences confrontation SpA lymphocytes, we used transgenic mice expressing fully Abs. We found that administration soluble reduces B-1a lymphocytes peritoneal cavity marginal zone spleen, resulting markedly deficient type 2 humoral...
Antibodies directed against the HIV-1 Envelope glycoprotein are routinely assessed for in vitro viral neutralization.The most commonly used assay is based on infection of a cell line that expresses luciferase upon by HIV-1.Recently, several groups have published techniques single-cell culture B cells 384-well plates.The standard 96 well neutralization format not suitable screening large number low-volume samples produced such cultures.Therefore, we adapted assays to "microneutralization"...
Some pathogens have evolved to produce proteins, called B-cell superantigens, that can interact with human immunoglobulin variable regions, independently of the combining site, and activate B lymphocytes express target immunoglobulins. However, in vivo consequences these interactions on numbers function are largely unknown. Using transgenic mice expressing fully immunoglobulins, we studied exposure protein L Peptostreptococcus magnus In mature pool cells, resulted a specific reduction...
Abstract Somatic hypermutation (SHM) of Ig genes depends upon the deamination C nucleotides in WRCY (W = A/T, R A/G, Y C/T) motifs by activation-induced cytidine deaminase (AICDA). Despite this, a large number mutations occur WA that can be accounted for activity polymerase η (POL η). To determine whether there are AICDA-independent and to characterize relationship between AICDA- POL η-mediated mutations, 1470 H chain 1313 κ- λ-chain rearrangements from three AICDA−/− patients were analyzed....
Thyroglobulin (Tg) measurements assess recurrence in post-thyroidectomy thyroid cancer patients. Tg by enzyme immunoassays (EIA) can be falsely elevated interference from autoantibodies (TgAb). Radioimmunoassay (RIA) is less susceptible to TgAb and has been the standard-of-care test for positive Recently developed liquid chromatography tandem mass spectrometry (LC–MS/MS) methods may eliminate interference. We assessed performance of EIA, RIA LC–MS/MS evaluate differences. measured 50 plasma...
Partitioning the human immunoglobulin variable region into (V), diversity (D), and joining (J) segments is a common sequence analysis step. We introduce novel approximate dynamic programming method that uses conserved gene motifs to improve performance of aligning V-segments rearranged (Ig) genes. Our new algorithm enhances former JOINSOLVER by processing sequences with insertions and/or deletions (indels) improves efficiency for large datasets provided high throughput sequencing. In our...