A5039697077- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Immune Response and Inflammation
- Monoclonal and Polyclonal Antibodies Research
- Ubiquitin and proteasome pathways
- vaccines and immunoinformatics approaches
- Macrophage Migration Inhibitory Factor
- PARP inhibition in cancer therapy
- Glycosylation and Glycoproteins Research
- HIV Research and Treatment
- Cancer Immunotherapy and Biomarkers
- Streptococcal Infections and Treatments
- Toxin Mechanisms and Immunotoxins
- Cytomegalovirus and herpesvirus research
- interferon and immune responses
- DNA Repair Mechanisms
- Diabetes and associated disorders
- Probiotics and Fermented Foods
- Cancer, Stress, Anesthesia, and Immune Response
- Calcium signaling and nucleotide metabolism
- Galectins and Cancer Biology
- Adipokines, Inflammation, and Metabolic Diseases
- Neonatal and Maternal Infections
- Trace Elements in Health
Université de Montréal
2013-2022
Université Laval
1990-2020
Centre d’Immunologie de Marseille-Luminy
2008
Institut National de la Recherche Scientifique
1993-2008
Institut Pasteur
1997-2005
Memorial Sloan Kettering Cancer Center
2005
Cornell University
2005
Bipar
2000
Montreal Clinical Research Institute
1993-1997
Stanford Medicine
1997
Abstract Solid tumours are innervated by nerve fibres that arise from the autonomic and sensory peripheral nervous systems 1–5 . Whether neo-innervation of pain-initiating neurons affects cancer immunosurveillance remains unclear. Here we show melanoma cells interact with nociceptor neurons, leading to increases in their neurite outgrowth, responsiveness noxious ligands neuropeptide release. Calcitonin gene-related peptide (CGRP)—one such nociceptor-produced neuropeptide—directly exhaustion...
In response to Toll-like receptor ligands, dendritic cells (DCs) dramatically enhance their antigen presentation capacity by stabilizing at the cell-surface MHC II molecules. We demonstrate here that, in human monocyte-derived DCs, RING-CH ubiquitin E3 ligase, membrane-associated I (MARCH I), promotes ubiquitination of HLA-DR beta-chain. Thus, nonactivated MARCH induces surface internalization mature complexes, therefore reducing stability and levels. further that maturation-dependent...
IL-10 is a potent anti-inflammatory cytokine interfering with antigen presentation by inducing the intracellular sequestration of MHC class II (MHC-II) molecules. Here we studied contribution membrane-associated RING-CH (MARCH) ubiquitin ligase family members to IL-10-induced down-regulation MHC-II We found that MARCH1 and MARCH8 proteins are most for surface expression in transfected cells, but only mRNA strongly induced human primary monocytes. detected mono- poly-ubiquitinated forms...
The success of immunotherapy relies on the participation all arms immune system and role CD4+ T lymphocytes in preventing tumor growth is now well established. Understanding how tumors evade responses holds key to development cancer immunotherapies. In this review, we discuss MHC Class II expression varies cells influences antitumor responses. We also means that are currently available for harnessing antigen presentation pathway efficient vaccines activate against cancer.
The staphylococcal enterotoxin A (SEA) is a superantigen that must bind to class II molecules of the major histocompatibility complex be recognized by T cells. In humans, most HLA-DR allelic and isotypic forms, such as DR1, SEA well. DRw53 an exception, binding very poorly. We have localized this difference single residue (amino acid 81) in beta 1 domain. highly conserved histidine at 81 allows binding, but tyrosine does not. Residue predicted lie alpha-helix on surface molecule, with its...
Abstract Insulin resistance is a key driver of type 2 diabetes (T2D) and characterized by defective insulin receptor (INSR) signalling. Although surface INSR downregulation well-established contributor to resistance, the underlying molecular mechanisms remain obscure. Here we show that E3 ubiquitin ligase MARCH1 impairs cellular action degrading cell INSR. Using large-scale RNA interference screen, identify as negative regulator March1 loss-of-function enhances, overexpression impairs,...
Abstract Ischemic myocardial injury results in sterile cardiac inflammation that leads to tissue repair, two processes controlled by mononuclear phagocytes. Despite global burden of cardiovascular diseases, we do not understand the functional contribution pathogenesis specific phagocyte lineages, particular dendritic cells. To address this limitation, used detailed lineage tracing and genetic studies identify bona fide murine human CD103+ conventional cell (cDC)1s, CD11b+ cDC2s, plasmacytoid...
Staphylococcal enterotoxin A (SEA) has two distinct binding sites for major histocompatibility complex (MHC) class II molecules. The aspartic acid located at position 227 (D227) in the COOH terminus of SEA is one three residues involved its interaction with DR beta chain, whereas phenylalanine 47 (F47) NH2 critical to alpha chain. Upon MHC molecules, triggers several cellular events leading cytokine gene expression. In present study, we have demonstrated that, contrary wild-type SEA,...
Major histocompatibility complex class II (MHC‐II) molecules accumulate in exocytic vesicles, called exosomes, which are secreted by antigen presenting cells. These vesicles released following the fusion of multivesicular bodies (MVBs) with plasma membrane. The molecular mechanisms regulating cargo selection remain to be fully characterized. As ubiquitination MHC‐II β‐chain cytoplasmic tail has recently been demonstrated various cell types, we sought determine if this post‐translational...
Superantigens bind to major histocompatibility complex class II molecules on antigen-presenting cells and stimulate T cells. Staphylococcus aureus enterotoxin B (SEB) toxic shock syndrome toxin-1 (TSST-1) the same region of human lymphocyte antigen (HLA)-DR1 but do not compete with each other, which indicates that they different subsets DR1 molecules. Here, a mutation in peptide-binding groove disrupted SEB TSST-1 binding sites, suggests peptides can influence interaction bacterial toxins....
Lipid rafts are plasma membrane microdomains that highly enriched in signaling molecules and act as signal transduction platforms for many immune receptors. The involvement of these HLA-DR-induced is less well defined. We examined the constitutive presence HLA-DR lipid rafts, their possible recruitment into microdomains, role responses. detected significant amounts EBV<sup>+</sup> EBV<sup>−</sup> B cell lines, monocytic transfected HeLa cells, tonsillar human monocytes. Localization was...
Some members of the membrane-associated RING-CH family E3 ubiquitin ligases (MARCHs) are membrane-bound and target major players immune response. MARCH1 ubiquitinates downregulates MHC class II expression in APCs. It is induced by IL-10 despite a strong increase mRNA human primary monocytes, protein remains hardly detectable. To gain insights into posttranslational regulation MARCH1, we investigated whether its itself regulated ubiquitination. Our results demonstrate that ubiquitinated...
Abstract Ubiquitination was recently identified as a central process in the pathogenesis and development of numerous inflammatory diseases, such obesity, atherosclerosis, asthma. Treatment with proteasomal inhibitors led to severe side effects because ubiquitination is heavily involved plethora cellular functions. Thus, new players regulating processes must be improve therapies for diseases. In addition their role adaptive immunity, endosomal MHC class II (MHCII) molecules were shown...
In a bead column experiment, attempts have been made to identify the proteins adsorbed from plasma onto glass surface. Proteins after 3-h contact time were eluted sequentially by 1 M tris buffer and SDS. Polyacrylamide gel electrophoresis of showed multiplicity components, not all these could be identified. Positive identifications immunodiffusion against specific antibodies, band positions on gels, location radioactivity in gels when radiolabeled added plasma. found albumin, IgG,...
Bacterial and retroviral superantigens (SAGs) stimulate a high proportion of T cells expressing specific variable regions the cell receptor (TCR) beta chain. Although most alleles isotypes bind SAGs, polymorphisms major histocompatibility complex (MHC) class II molecules affect their presentation to cells. This observation has raised possibility that TCR-MHC interaction can occur during this recognition process. To address importance such interactions SAG presentation, we have used panel...
Major histocompatibility complex (MHC) class II molecules are highly polymorphic and bind peptides for presentation to CD4+ T cells. Functional adhesion assays have shown that CD4 interacts with MHC molecules, leading enhanced responses of cells after the activation CD4-associated tyrosine kinase p56lck. We addressed possible contribution allelic polymorphism in interaction between molecules. Using mouse DAP-3-transfected expressing different isotypes forms HLA-DR molecule, we a functional...
Bacterial superantigens (SAgs) bind to major histocompatibility complex (MHC) class II molecules and activate T cells in a Vβ-restricted fashion. We recently identified subsets of HLA-DR1 that show selectivity for SAgs. Here, we extend these observations by showing different cell lineages demonstrate distinct SAg-binding specificities although they all express HLA-DR1. Indeed, B staphylococcal enterotoxin A (SEA) toxic shock syndrome toxin 1 (TSST-1) with high affinity while (SEB) binding is...
ABSTRACT Human immunodeficiency virus type 1 (HIV-1) assembly, budding, and release occur mostly at the plasma membrane in T lymphocytes as well established nonlymphoid cell lines, while macrophages these processes primarily intracellular compartments that harbor late endosomal/multivesicular body (LE/MVB) markers, including human leukocyte antigen DR (HLA-DR). Major histocompatibility complex class II molecules (MHC-II), which are expressed activated cells, have been previously reported to...
Bovine whey from the cheese-making industry contains several bioactive factors that promote health and prevent disease. Although many efforts have been made over years to show immunoglobulins, lactoperoxidase, lactoferrin, lysosyme small peptides present in antimicrobial activities against pathogenic microorganisms, such not investigated so far for lipid fraction of whey. Here, we used an vitro assay-based fractionation procedure free fatty acids derived cream specifically inhibit...