A5038501139- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- HIV Research and Treatment
- vaccines and immunoinformatics approaches
- HIV/AIDS drug development and treatment
- Diabetes and associated disorders
- CAR-T cell therapy research
- Rheumatoid Arthritis Research and Therapies
- Receptor Mechanisms and Signaling
- Metal-Catalyzed Oxygenation Mechanisms
- Cancer Immunotherapy and Biomarkers
- Food Allergy and Anaphylaxis Research
- Systemic Lupus Erythematosus Research
- Allergic Rhinitis and Sensitization
- S100 Proteins and Annexins
- Vector-borne infectious diseases
- Inorganic Chemistry and Materials
- 14-3-3 protein interactions
- Spectroscopy and Quantum Chemical Studies
- Biosimilars and Bioanalytical Methods
- HIV-related health complications and treatments
- Protease and Inhibitor Mechanisms
- Photosynthetic Processes and Mechanisms
Benaroya Research Institute
2016-2024
Virginia Mason Medical Center
2016-2024
Anocca (Sweden)
2023
Karolinska University Hospital
2010-2020
Karolinska Institutet
2010-2020
Science for Life Laboratory
2013-2020
Centre for Inflammation Research
2017
Uppsala University
2008
Max Planck Institute for Biophysical Chemistry
2007
Max Planck Institute for Chemical Ecology
2006
Neutrophil extracellular traps containing citrullinated peptides promote inflammation in synovial fibroblasts.
In response to herbivore (Spodoptera littoralis) attack, lima bean (Phaseolus lunatus) leaves produced hydrogen peroxide (H(2)O(2)) in concentrations that were higher when compared mechanically damaged (MD) leaves. Cellular and subcellular localization analyses revealed H(2)O(2) was mainly localized MD herbivore-wounded (HW) zones spread throughout the veins tissues. Preferentially, found cell walls of spongy mesophyll cells facing intercellular spaces, even though confocal laser scanning...
Oxygen formation was detected for the oxidations of various multinuclear manganese complexes by oxone (HSO5−) in aqueous solution. To determine to what extent water source evolved O2, H218O isotope-labelling experiments coupled with membrane inlet mass spectrometry (MIMS) were carried out. We discovered that during reaction [Mn2(OAc)2(bpmp)]+ (1), stoichiometrically labelled oxygen (18O2) formed. This is first example a homogeneous mediated synthetic complex where addition strong chemical...
Antibodies to citrullinated proteins, common in rheumatoid arthritis (RA) patients, are strongly associated a specific set of HLA-DR alleles including HLA-DRB1*04:01, *04:04, and *01:01. Here, we first demonstrate that autoantibody levels toward the dominant B cell epitope from α-enolase significantly elevated HLA-DRB1*04:01-positive RA patients. Furthermore, identified α-enolase-derived T epitopes demonstrated native versions several peptides bind with different affinities The citrulline...
The intracellular trafficking of major histocompatibility complex class I (MHC-I) proteins is directed by three quality control mechanisms that test for their structural integrity, which correlated to the binding high-affinity antigenic peptide ligands. To investigate molecular features MHC-I these detect, we have followed hypothesis suboptimally loaded are characterized conformational mobility in F pocket region site. We created a novel variant an protein, Kb-Y84C, two alpha helices this...
Abstract MHC tetramers are an essential tool for characterizing antigen-specific CD4+ T cells. However, their ex vivo analysis is limited by the large sample requirements. Here we demonstrate a combinatorial staining approach that allows simultaneous characterization of multiple specificities to address this challenge. As proof principle, analyse T-cell responses seasonal influenza vaccine, establishing frequency hierarchy and examining differences in memory activation status, lineage...
Recognition of citrullinated antigens such as vimentin, fibrinogen, and α-enolase is associated with rheumatoid arthritis (RA). Emerging data suggest that the matrix protein aggrecan also recognized a antigen. This study was undertaken to directly visualize Cit-aggrecan-specific T cells characterize them in patients RA.Citrullinated peptides likely DRB1*04:01 binding motifs were predicted using previously published scanning algorithm. Peptides detectable assessed for immunogenicity by HLA...
The obligate intracellular parasite Toxoplasma gondii exploits cells of the immune system to disseminate. Upon infection, parasitized dendritic (DCs) and microglia exhibit a hypermigratory phenotype in vitro that has been associated with enhancing dissemination vivo mice. One unresolved question is how parasites commandeer achieve systemic by 'Trojan-horse' mechanism. By chromatography mass spectrometry analyses, we identified an orthologue 14-3-3 protein family, T. (Tg14-3-3), as mediator...
HLA class II tetramers can be used for ex vivo enumeration and phenotypic characterisation of antigen-specific CD4+ T cells. They are increasingly applied in settings like allergy, vaccination autoimmune diseases. Rheumatoid arthritis (RA) is a chronic disorder which many autoantigens have been described.Using multi-parameter flow cytometry, we developed multi-HLA tetramer approach to simultaneously study several antigen specificities RA patient samples. We focused on previously described...
Background Induction of broadly neutralizing antibodies, such as the monoclonal antibodies IgGb12, 2F5 and 2G12, is objective most antibody-based HIV-1 vaccine undertakings. However, despite relative conserved nature epitopes targeted by these mechanisms underlying sensitivity circulating variants to are not fully understood. Here we have studied that emerge during disease progression in relation molecular alterations viral envelope glycoproteins (Env), using a panel primary R5 isolates...
Exhausted CD8 T cells (T
Background Dog dander extract used for diagnosis and allergen-specific immunotherapy is often of variable poor quality. Objective To assemble four well-established dog allergen components into one recombinant folded protein improved vaccination allergy to dog. Methods A linked molecule, comprising the lipocalin allergens Can f 1, 2, 4 6 was constructed. The tetrameric structurally characterized by small angle X-ray scattering, compared with each single or an equimolar mix analytical size...
The immunogenicity of H ‐2 D b ( ) restricted epitopes can be significantly increased by substituting peptide position 3 to a proline (p3 P ). p3 modification enhances MHC stability without altering the conformation modified epitope allowing for T ‐cell cross‐reactivity with native peptide. present study reveals how specific interactions between and highly conserved heavy chain residue Y 159 increase in complex an optimized version melanoma‐associated gp100 25–33 . Furthermore, directly...
Abstract Novel, exciting intervention strategies to prevent infection with HIV have been tested in the past year, and field is rapidly evolving. EUROPRISE a network of excellence sponsored by European Commission concerned wide range activities including integrated developmental research on vaccines microbicides from discovery early clinical trials. A central timely theme development unique concept co-usage microbicides. This review, prepared PhD students captures much ongoing between...
Leukocyte Ig-like receptor (LIR) 1 (CD85j/ILT2/LILRB1) is an inhibitory with broad specificity for MHC class I (MHC-I) and the human CMV MHC-I homologue UL18. LIR-1 can inhibit NK cells through conventional interaction expressed on a target cell (in trans) but nature effects of interactions in cis are not well understood. Here we show that has impact detection various antibodies. We found alters recognition by only one two antibodies known to block functional trans cells. Specifically,...
Viral escape from CD8+ cytotoxic T lymphocyte responses correlates with disease progression and represents a significant challenge for vaccination. Here, we demonstrate that cell recognition of the naturally occurring MHC-I-restricted LCMV-associated immune variant Y4F is restored following vaccination proline-altered peptide ligand (APL). The APL increases MHC/peptide (pMHC) complex stability, rigidifies facilitates receptor (TCR) through reduced entropy costs. Structural analyses pMHC...
Abstract Tick-borne encephalitis virus (TBEV) is a leading cause of viral meningoencephalitis in many parts Europe and eastwards Asia, with high morbidity often long-term neurologic sequelae. With no treatment available, studies the immune response to TBEV are essential for understanding immunopathogenesis tick-borne development therapeutics. We have previously demonstrated that CD8+ T cell responses peripheral blood patients acute peak at around 7 d after hospitalization neuroinvasive phase...
Abstract Rheumatoid arthritis (RA) is associated with high-risk HLA class II alleles known as the “RA shared epitope.” Among prevalent epitope alleles, study of DRB1*04:04 has been limited. To define relevant epitopes, we identified citrullinated peptide sequences from synovial antigens that were predicted to bind HLA-DRB1*04:04 and utilized a systematic approach confirm their binding assess recognition by CD4 T cells. After confirming immunogenicity 13 peptides derived aggrecan, cartilage...
Neutralizing antibodies (NAb) able to react heterologous viruses are generated during natural HIV-1 infection in some individuals. Further knowledge is required order understand the factors contributing induction of cross-reactive NAb responses. Here a well-established model experimental pathogenic cynomolgus macaques, which reproduces long-lasting infection, was used study response as well viral evolution highly neutralization-resistant SIVmac239. Twelve animals were infected intravenously...
The molecular basis underlying T-cell recognition of MHC molecules presenting altered peptide ligands is still not well-established. A hierarchy activation by class I-restricted has been defined using the receptor P14 specific for H-2D(b) in complex with immunodominant lymphocytic choriomeningitis virus gp33 (KAVYNFATM). While substitution tyrosine to phenylalanine (Y4F) or serine (Y4S) abolished P14, TCR unexpectedly recognized alanine-substituted semiagonist Y4A, which displayed most...
7C8 is a mouse monoclonal antibody specific for the third hypervariable region (V3) of human immunodeficiency virus type 2 (HIV-2)-associated protein gp125. The three-dimensional crystal structure Fab fragment 7C8, determined to 2.7 Å resolution, reveals deep and narrow antigen-binding cleft with architecture appropriate an elongated epitope. highly hydrophobic bordered on one side by negatively charged second complementarity determining (CDR2) unusually long positively CDR3 heavy chain and,...
Our knowledge of the binding sites for neutralizing Abs (NAb) that recognize a broad range HIV-1 strains (bNAb) has substantially increased in recent years. However, gaps remain our understanding how to focus B cell responses vulnerable conserved within envelope glycoprotein (Env). In this article, we report an immunization strategy composed trivalent (clade envs) DNA prime, followed by SIVmac239 gp140 Env protein boost aimed immune response structurally parts and simian immunodeficiency...