37 research outputs found
Association of distinct tetraspanins with MHC class II molecules at different subcellular locations in human immature dendritic cells
Dendritic cells have the capacity to trigger T cell responses in lymphoid organs against antigens captured in the periphery. T cell stimulation depends on the ability of MHC class II molecules to present peptides at the cell surface that are acquired in MHC class II compartments. The high capacity of dendritic cells to stimulate T lymphocytes is related to their ability to regulate the distribution of MHC class II molecules intracellularly. To analyze the molecular components involved in the generation of MHC class II-peptide complexes in human immature dendritic cells, mAb were raised against purified MHC class II compartments. One of the antigens turned out to be CD63, a member of the tetraspanin superfamily. CD63 localized exclusively intracellularly where it associated with peptide-loaded class II molecules. In contrast, the tetraspanins CD9, CD53 and CD81 associated with class II molecules at the plasma membrane. Selective association of distinct tetraspanins may be involved in the regulation of MHC class II distribution in human dendritic cell
Association of distinct tetraspanins with MHC class II molecules at different subcellular locations in human immature dendritic cells
Twee watervoerende lagen met semi-doorlatende scheidings- en afdeklaag: Tijdsafhankelijke grondwaterstroming onder dijken ten behoeve van een peilbuizennet langs Nederlandse rivieren
In het kader van het onderzoek van een peilbuizennet langs de nederlandse rivieren, is er een studie uitgevoerd naar de effecten van een geinstalleerde bron in een twee-lagen systeem; een watervoerende zandlaag en een afdekkende klei- of veenlaag [2],[3]. In dit rapport wordt aan de hand van bovengenoemde studie, de vergelijkingen beschreven van twee watervoerende zandlagen, gescheiden en afgedekt door consoliderende klei- of veenlagen (zie figuur 1). Het verkregen stelsel differentiaalvergelijkingen wordt Laplace getransformeerd en opgelost. De terug transformatie in de tijd moet dan gebeuren m.b.v- de direkte methode [2]. Aangetoond wordt dat de oplossing reële wortels heeft, zowel vlaksymmetrisch als axiaal symmetrisch.TAW/EN
Differential intracellular fate of Burkholderia pseudomallei 844 and Burkholderia thailandensis UE5 in human monocyte-derived dendritic cells and macrophages
Abstract Background Burkholderia pseudomallei (Bp) is a category B biothreat organism that causes a potentially fatal disease in humans and animals, namely melioidosis. Burkholderia thailandensis (Bt) is another naturally occurring species that is very closely related to Bp. However, despite this closely related genotype, Bt is considered avirulent as it does not cause the disease. In the present study, we compared the growth kinetics of B. pseudomallei strain 844 (Bp-844) in human monocyte-derived dendritic cells (MoDCs) and macrophages (Mφs), as well as its ability to stimulate host cell responses with those of B. thailandensis strain UE5 (Bt-UE5). Results Primary human MoDCs and Mφs were infected with Bp-844 and its intracellular growth kinetics and ability to induce host cell responses were evaluated. The results were compared with those obtained using the Bt-UE5. In human MoDCs, both bacteria were similar in respect to their ability to survive and replicate intracellularly, induce upregulation of costimulatory molecules and cytokines and bias T helper cell differentiation toward a Th1 phenotype. By contrast, the two bacteria exhibited different growth kinetics in human Mφs, where the intracellular growth of Bt-UE5, but not Bp-844, was significantly suppressed. Moreover, the ability of Mφs to kill Bp-844 was markedly enhanced following stimulation with IFN-γ. Conclusion The data presented showed that while both strains were similar in their ability to survive and replicate in human MoDCs, only Bp-844 could readily replicate in human Mφs. Both bacteria induced similar host cellular responses, particularly with regard to their ability to bias T cell differentiation toward a Th1 phenotype.</p
Differential post-translational modification of CD63 molecules during maturation of human dendritic cells
The capacity of dendritic cells to initiate T cell responses is related to their ability to redistribute MHC class II molecules from the intracellular MHC class II compartments to the cell surface. This redistribution occurs during dendritic cell development as they are converted from an antigen capturing, immature dendritic cell into an MHC class II-peptide presenting mature dendritic cell. During this maturation, antigen uptake and processing are down-regulated and peptide-loaded class II complexes become expressed in a stable manner on the cell surface. Here we report that the tetraspanin CD63, that associates with intracellularly localized MHC class II molecules in immature dendritic cells, was modified post-translationally by poly N-acetyl lactosamine addition during maturation. This modification of CD63 was accompanied by a change in morphology of MHC class II compartments from typical multivesicular organelles to structures containing densely packed lipid moieties. Post-translational modification of CD63 may be involved in the functional and morphological changes of MHC class II compartments that occur during dendritic cell maturation
Immune escape through C-type lectins on dendritic cells
Dendritic cells (DCs) detect different pathogens and elicit tailored anti-microbial immune responses. They express C-type lectins that recognise carbohydrate profiles on microorganisms, resulting in internalisation, processing and presentation. Intracellular sequences of distinct DC-specific lectins point to differences in intracellular routing that influence antigen presentation. Moreover, putative signalling motifs hint to the activation of DCs on carbohydrate recognition. Recent evidence shows that not only pathogens, but also tumour antigens, exploit C-type lectins to escape intracellular degradation resulting in abortive immunity. More insight into ligand specificity, intracellular targeting and signalling will reveal the pathways by which pathogens modulate immunity through C-type lectin
DC-SIGN, a C-type lectin on dendritic cells that unveils many aspects of dendritic cell biology
Dendritic cells (DC) are present in essentially every tissue where they operate at the interface of innate and acquired immunity by recognizing pathogens and presenting pathogen-derived peptides to T cells. It is becoming clear that not all C-type lectins on DC serve as antigen receptors recognizing pathogens through carbohydrate structures. The C-type lectin DC-SIGN is unique in that it regulates adhesion processes, such as DC trafficking and T-cell synapse formation, as well as antigen capture. Moreover, even though several C-type lectins have been shown to bind HIV-1, DC-SIGN does not only capture HIV-1 but also protects it in early endosomes allowing HIV-1 transport by DC to lymphoid tissues, where it enhances trans infection of T cells. Here we discuss the carbohydrate/protein recognition profile and other features of DC-SIGN that contribute to the potency of DC to control immunit
