A5041719537- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- HIV Research and Treatment
- Click Chemistry and Applications
- vaccines and immunoinformatics approaches
- Chemical Synthesis and Analysis
- Pneumonia and Respiratory Infections
- Allergic Rhinitis and Sensitization
- Cytomegalovirus and herpesvirus research
- Glycosylation and Glycoproteins Research
- HIV/AIDS drug development and treatment
- Contact Dermatitis and Allergies
- Mosquito-borne diseases and control
- CAR-T cell therapy research
- Pneumocystis jirovecii pneumonia detection and treatment
- Food Allergy and Anaphylaxis Research
- Streptococcal Infections and Treatments
- Protein Structure and Dynamics
- Cancer Immunotherapy and Biomarkers
- Receptor Mechanisms and Signaling
- Systemic Lupus Erythematosus Research
- interferon and immune responses
- Peptidase Inhibition and Analysis
Lebanese University
2025
Science for Life Laboratory
2015-2024
Karolinska University Hospital
2014-2024
Karolinska Institutet
2015-2024
Hôpital Sahloul
2021
Svenska Örtmedicinska Institute
2013-2020
Hospital Fatuma Bourguiba Monastir
2020
Université de Bretagne Occidentale
2016
Centre Hospitalier Régional Universitaire de Brest
2015-2016
Université Européenne de Bretagne
2016
Abstract SARS-CoV-2 enters host cells through an interaction between the spike glycoprotein and angiotensin converting enzyme 2 (ACE2) receptor. Directly preventing this presents attractive possibility for suppressing replication. Here, we report isolation characterization of alpaca-derived single domain antibody fragment, Ty1, that specifically targets receptor binding (RBD) spike, directly ACE2 engagement. Ty1 binds RBD with high affinity, occluding ACE2. A cryo-electron microscopy...
Inflammatory response induced by microglia plays a critical role in the demise of neuronal populations neuroinflammatory diseases. Although toll-like receptor 4 (TLR4) microglia's inflammatory is fully acknowledged, little known about endogenous ligands that trigger TLR4 activation. Here, we report galectin-3 (Gal3) released acts as an paracrine ligand. Gal3-TLR4 interaction was further confirmed murine model (intranigral lipopolysaccharide [LPS] injection) and human stroke subjects....
Human histocompatibility leukocyte antigen (HLA)-E is a nonclassical major complex (MHC) class I molecule which presents restricted set of nonameric peptides, derived mainly from the signal sequence other MHC molecules. It interacts with CD94/NKG2 receptors expressed on surface natural killer (NK) cells and T cell subsets. Here we demonstrate that HLA-E also peptide leader human heat shock protein 60 (hsp60). This gains access to intracellularly, resulting in up-regulated HLA-E/hsp60...
The Ras-GAP SH3 domain–binding proteins (G3BP) are essential regulators of the formation stress granules (SG), cytosolic aggregates and RNA that induced upon cellular stress, such as virus infection. Many viruses, including Semliki Forest (SFV), block SG induction by targeting G3BP. In this work, we demonstrate G3BP-binding motif SFV nsP3 consists two FGDF motifs, in which both phenylalanine glycine residue for binding. addition, show binding partner USP10 is also mediated an motif....
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease, which exhibits multiple B cell abnormalities including expanded populations of memory cells and elevated levels autoantibodies. Belimumab monoclonal antibody targeting the cytokine BAFF (a.k.a. BLyS), approved for treatment SLE.In this prospective cohort study, from peripheral blood 23 SLE patients initiating belimumab followed longitudinally up to three years, were assessed using mass cytometry.B decreased during study...
Post-translational modifications (PTMs) constitute a major aspect of protein biology, particularly signaling events. Conversely, several different pathophysiological PTMs are hallmarks oxidative imbalance or inflammatory states and strongly associated with pathogenesis autoimmune diseases cancers. Accordingly, it is interest to assess both the biological structural effects modification. For latter, computer-based modeling offers an attractive option. We thus identified need for easily...
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...
In pulmonary sarcoidosis, CD4 + T-cells expressing T-cell receptor Vα2.3 accumulate in the lungs of HLA-DRB1*03 patients. To investigate receptor-HLA-DRB1*03 interactions underlying recognition hitherto unknown antigens, we performed detailed analyses expression on bronchoalveolar lavage fluid from sarcoidosis Pulmonary patients (n=43) underwent bronchoscopy with lavage. α and β chains were analysed by flow cytometry, DNA-sequenced, three-dimensional molecular models complexes generated....
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...
Tumor cells frequently escape from CD8+ T cell recognition by abrogating MHC-I antigen presentation. Deficiency in processing components, like the transporter associated with (TAP), results strongly decreased surface display of peptide/MHC-I complexes. We previously identified a class hidden self-antigens known as epitopes impaired peptide (TEIPP), which emerge on tumor such defects. In present study, we analyzed thymus selection and peripheral behavior specificity for prototypic TEIPP...
Recent findings have highlighted the role of Old World alphavirus non-structural protein 3 (nsP3) as a host defence modulator that functions by disrupting stress granules, subcellular phase-dense RNA/protein structures formed upon environmental stress. This disruption mechanism was largely explained through nsP3-mediated recruitment G3BP via two tandem FGDF motifs. Here, we present 1.9 Å resolution crystal structure NTF2-like domain G3BP-1 in complex with 25-residue peptide derived from...
The cytosolic N-acetylmuramoyl-l-alanine amidase LytA protein of Streptococcus pneumoniae, which is released by bacterial lysis, associates with the cell wall via its choline-binding motif. During exponential growth, accesses peptidoglycan substrate to cause lysis only when nascent synthesis stalled nutrient starvation or β-lactam antibiotics. Here we present three-dimensional structures and establish requirements for binding catalytic activity. solution structure full-length dimer reveals a...
In the era towards precision medicine, we here present individual specific autoantibody signatures of 193 healthy individuals. The self-reactive IgG are stable over time in a way that each profile is recognized longitudinal sampling. reactivity an antigen array comprising 335 protein fragments, representing 204 human proteins with potential relevance to autoimmune disorders, was measured plasma samples from This analysis resulted unique barcodes for were maintained one year's time. profiles,...
Humoral immunity is important in limiting clinical disease malaria, yet the longitudinal B cell response to infection remains unclear. We performed a 1-year prospective study patients treated for acute P. falciparum malaria first time, or with previous exposure disease. Using an unbiased exploratory approach mass cytometry, followed by targeted flow we found that ~80% of mature cells proliferated expressed CD11c. Only ~40% CD11c+ displayed atypical phenotype, remaining primarily made up...
The domestic cat (Felis domesticus) is one of the most important causes allergic asthma worldwide. dominating allergen, Fel d 1, composed two heterodimers. Recently, it has been shown that recombinant consisting chain 2 and 1 fused together without additional linker, immunological properties indistinguishable from natural heterodimeric protein. Herein, we report crystal structure monomeric at 1.85-A resolution, determined by multi-wavelength anomalous diffraction using selenomethionine...
Abstract Immunogenicity of tumor-associated antigens (TAA) is often weak because many TAA are autoantigens for which the T-cell repertoire sculpted by tolerance mechanisms. Substitutions at main anchor positions to increase complementarity between peptide and MHC class I (MHC-I) binding cleft constitute a common procedure improve capacity immunogenicity TAA. However, such alterations tailored each MHC-I allele may recruit different CTL specificities through conformational changes in targeted...
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...
The 14-3-3 molecular scaffolds promote type I interferon (IFN) responses by stabilizing the interaction of RIG-I with TRIM25 ligase. Viruses have evolved unique strategies to halt this cellular response support their replication and spread. Here, we report that ubiquitin deconjugase (DUB) encoded in N-terminus Epstein-Barr virus (EBV) large tegument protein BPLF1 harnesses molecules autoubiquitination sequestration ligase into inactive aggregates. Catalytically induced K48-linked degradation...
Autoantibodies targeting histidyl-transfer RNA synthetase (HisRS; anti-Jo-1) are common in the idiopathic inflammatory myopathies (IIMs) and antisynthetase syndrome. This study was undertaken to investigate immunity against HisRS blood lungs of patients with IIM/antisynthetase syndrome.Bronchoalveolar lavage (BAL) fluid, BAL fluid cells, peripheral mononuclear cells (PBMCs) from syndrome (n = 24) were stimulated full-length protein or a HisRS-derived peptide (HisRS11-23 ). PBMCs sarcoidosis...
MHC-I epitope presentation to CD8+ T cells is directly dependent on peptide loading and selection during antigen processing. However, the exact molecular bases underlying binding by remain largely unknown. Within peptide-loading complex, editor tapasin key of MHC-I-bound peptides. Here, we have determined an ensemble crystal structures in complex with exchange-associated dipeptide GL, as well tapasin-associated scoop loop, alone or combination candidate epitopes. These results combined...
Abstract SARS-CoV-2 is the etiologic agent of COVID-19, currently causing a devastating pandemic for which pharmacological interventions are urgently needed. The virus enters host cells through an interaction between spike glycoprotein and angiotensin converting enzyme 2 (ACE2) receptor. Directly preventing this presents attractive possibility suppressing replication. Here we report isolation characterization alpaca-derived single domain antibody fragment, Ty1, that specifically targets...
Murine natural killer (NK) cells are inhibited from killing their targets by the interaction between inhibitory, C-type lectin like Ly49 receptors and major histocompatibility complex (MHC) class I molecules. The have overlapping specificity, it has been difficult to analyze specific aspects of different respective ligands. We addressed this problem using tetramers bacterially expressed, non-glycosylated, MHC molecules refolded with peptides. Our results indicate that technology is useful...