A5068619290- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- HIV Research and Treatment
- Parasitic Diseases Research and Treatment
- Influenza Virus Research Studies
- Immune Response and Inflammation
- Complement system in diseases
- RNA Interference and Gene Delivery
- Pluripotent Stem Cells Research
- vaccines and immunoinformatics approaches
- Phagocytosis and Immune Regulation
- CAR-T cell therapy research
- Glycosylation and Glycoproteins Research
- Herpesvirus Infections and Treatments
- Toxin Mechanisms and Immunotoxins
- HIV/AIDS drug development and treatment
- Genetics, Aging, and Longevity in Model Organisms
- Mosquito-borne diseases and control
- Toxoplasma gondii Research Studies
- Parasites and Host Interactions
- Bacteriophages and microbial interactions
- Respiratory viral infections research
- Bacterial Genetics and Biotechnology
University of Wisconsin–Madison
2017-2024
Theraclone Sciences (United States)
2010
Vanderbilt University
2000-2004
Celltechgen (United States)
2004
Howard Hughes Medical Institute
1992-2001
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa
1997-1999
Fred Hutch Cancer Center
1995
University of Washington
1992-1994
University of California, San Diego
1993
New England Biolabs (United States)
1988-1992
Major histocompatibility complex (MHC) class I molecules bind peptides that are delivered from the cytosol into endoplasmic reticulum by MHC-encoded transporter associated with antigen processing (TAP). Peptide capture immature heterodimers of heavy chains and beta 2-microglobulin may be facilitated their physical association TAP. A genetic defect in a human mutant cell line causes complete failure diverse to associate This deficiency impairs ability efficiently results loss function an...
Influenza remains a serious public health threat throughout the world. Vaccines and antivirals are available that can provide protection from infection. However, new viral strains emerge continuously because of plasticity influenza genome, which necessitates annual reformulation vaccine antigens, resistance to appear rapidly become entrenched in circulating virus populations. In addition, spread pandemic is difficult contain time required engineer manufacture effective vaccines. Monoclonal...
Fc-mediated antibody effector functions, such as antibody-dependent cellular cytotoxicity (ADCC), can contribute to the containment HIV-1 replication but whether activities are sufficient for protection is unclear. We previously identified an variable 2 (V2) apex of Env trimer (PGT145) that potently directs lysis SIV-infected cells by NK poorly neutralizes SIV infectivity. To determine if ADCC protection, separate groups six rhesus macaques were treated with PGT145 or a control (DEN3)...
ABSTRACT Anti-HIV-1 antibodies capable of mediating ADCC are elicited by the majority people with HIV-1 and preferentially target “open,” CD4-bound conformation envelope glycoproteins (Env). However, due to “closed” sampled unliganded HIV-1-Envs, these ineffective at eliminating infected cells. BNM-III-170 is a small-molecule CD4-mimetic compound that binds Phe43 cavity gp120 subunit Env, forcing Env “open up,” thus exposing epitopes targeted CD4-induced (CD4i), ADCC-mediating antibodies....
We have cloned and sequenced the predominant germline V kappa gene segment expressed by B cells of strain A origin that synthesize antibodies with specificity for Ars. In hybridomas synthesizing anti-Ars antibodies, this (V IdCR) has been found exclusively associated J 1 without exhibiting junctional sequence variation. Sequence comparisons IdCR derivatives reveals latter frequently contain somatically introduced amino acid replacements. Taken together results previous structural analyses,...
An unusual antigen composed of tandemly repeated protein units was cloned from the filarial parasite Dirofilaria immitis. The initially identified by screening a lambda gt11 cDNA library with serum dogs immunized irradiated D. immitis third-stage larvae. DNA sequence analysis clone, Di5, revealed continuous open reading frame two 399-base-pair repeats arranged in tandem. Southern blot genomic showed that gene coding for Di5 is tandem array 25-50 copies this same repeat. Antiserum raised...
Alternate class I MHC (MHC-I) Ag processing via cytosolic or vacuolar pathways leads to cross-presentation of exogenous CD8 T cells. Vacuolar alternate MHC-I involves phagolysosomal proteolysis and peptide binding in post-Golgi compartments. We report the first study tapasin(-/-) cells experiments with TAP1(-/-) macrophages that characterize processing. Tapasin promotes retention endoplasmic reticulum (ER) for loading high affinity peptides, whereas allow poorly loaded molecules exit ER....
Abstract Using a mouse mutagenesis screen, we have identified CD83 as being critical for the development of CD4+ T cells and their function postactivation. CD11c+ dendritic develop normally in mice with mutated gene but cell is substantially reduced. Additionally, now show that those mutant animal fail to respond following allogeneic stimulation. This at least part due an altered cytokine expression pattern characterized by increased production IL-4 IL-10 diminished IL-2 production. Thus,...
Abstract The T cell receptor (TcR) on CD8 + lymphocytes recognizes a complex which consists of major histocompatibility (MHC) heavy chain, β2‐microglobulin (β 2 M), and peptide the surface antigen‐presenting cells. Mutational analyses have suggested that TcR both αl α2 domains chain as well peptide. In light this, it is interest to know what extent take distinct conformations when bound individual peptides. It has recently been shown antibodies recognize K b MHC are sensitive peptides in...
We describe a novel method for screening large libraries of random peptides T cell antigens. Two were constructed, containing fixed amino acids representing the major histocompatibility complex (MHC) class I anchor residues H-2Kb-restricted octamers and H-2Db-restricted nonamers. Peptides from Kb-restricted library (KbL: SXIXFXXL) Db-restricted (DbL: XXXXNXXXIM) specifically stabilize empty Kb Db molecules, respectively. The contain that mimic several H-2b-restricted cytotoxic lymphocyte...
Single-residue changes were introduced into the murine major histocompatibility complex class I molecule H-2Kb at positions 65 and 69, which are predicted to point up from alpha-helix of alpha 1 domain not peptide binding groove. Mutated wild-type genes transfected cell line P815 (H-2d). We present evidence that did affect three foreign peptides recognized by cytotoxic T lymphocytes (CTL) in association with H-2Kb. Additionally, mutants provoked strong alloreactive responses cells mice...
Abstract H2-M3 is a class Ib MHC molecule that binds highly restricted pool of peptides, resulting in its intracellular retention under normal conditions. However, addition exogenous M3 ligands induces escape from the endoplasmic reticulum (ER) and, ultimately, expression at cell surface. These features make it powerful and novel model system to study potentially interrelated functions ER-resident I chaperone tapasin. The ascribed tapasin include: 1) ER peptide-empty molecules, 2) TAP...
Abstract Presentation of antigenic peptides to T lymphocytes by MHC class I molecules is regulated events involving multiple endoplasmic reticulum proteins, including tapasin. By studying the effects substitutions in tapasin Ig-like domain, we demonstrated that H-2Ld/tapasin association can be segregated from reconstitution folded Ld surface expression. This finding suggests peptide acquisition influenced functions are independent binding. We also found presence a nine-amino acid region...
As a consequence of their independent evolutionary origins in apes and Old World monkeys, human immunodeficiency virus type 1 (HIV-1) simian viruses the SIV
Abstract The loading of MHC class I molecules with peptides involves a variety accessory proteins, including TAP-associated glycoprotein (tapasin), which tethers empty to the TAP peptide transporter. We have evaluated role tapasin for assembly Ib molecule Qa-1b. In normal cells, Qa-1b is predominantly bound by peptide, Qa-1 determinant modifier (Qdm), derived from signal sequence Ia molecules. Our results show that links transporter, and facilitates delivery cell surface. Tapasin was also...
Abstract The rhesus macaque is an important animal model for AIDS and other infectious diseases; however, studies to address NK cell function in this species have been limited by the lack of defined ligands killer Ig-like receptors (KIRs). To identify KIRs, we adopted a novel approach based on pair stable lines. NFAT-responsive luciferase reporter lines expressing extracellular domains KIRs fused transmembrane cytoplasmic CD28 CD3ζ were incubated with target cells individual MHC class I...