Search results for "MHC"
showing 10 items of 233 documents
The use of clonal mRNA as an antigenic format for the detection of antigen-specific T lymphocytes in IFN-gamma ELISPOT assays.
2003
Abstract Most assay systems for the quantification of antigen-specific T-cell responses in infectious, malignant and autoimmune disease depend on the peptide antigen format and are therefore restricted to known epitopes and their presenting HLA molecules. Here we tested in ELISPOT assays the application of in vitro-transcribed clonal mRNA as an alternative antigen format covering all potential epitopes of a given antigen. As model antigens, we chose pp65 of human cytomegalovirus (HCMV) and human tyrosinase (hTyr). Antigen-presenting cells (APC) were K562 cells stably transfected with single HLA class I alleles and autologous dendritic cells (DC). As effectors, we applied in vitro-generated …
Mechanical Regulation of the Cytotoxic Activity of Natural Killer Cells
2020
AbstractMechanosensing has been recently explored for T cells and B cells and is believed to be part of their activation mechanism. Here, we explore the mechanosensing of the third type of lymphocytes – Natural Killer (NK) cells, by showing that they modulate their immune activity in response to changes in the stiffness of a stimulating surface. Interestingly, we found that this immune response is bell-shaped, and peaks for a stiffness of a few hundreds of kPa. This bell-shape behavior was observed only for surfaces functionalized with the activating ligand MHC class I polypeptide-related sequence A (MICA), but not for control surfaces lacking immunoactive functionalities. We found that sti…
Cloning and functional analyses of the mouse tapasin promoter
2003
The expression of tapasin is critical for an optimized MHC class I assembly and stable MHC class I surface expression. Thus, impaired MHC class I antigen expression of tumors can be attributable to tapasin downregulation. In order to understand the molecular mechanisms of deficient tapasin expression, the mouse tapasin promoter region and its 5'-flanking sequences were characterized. The mouse tapasin promoter lacks the TATA box and its transcription is initiated at multiple sites within a 51-nucleotide stretch. Sequence analyses revealed transcription factor binding motifs for NF-kappaB, GATA, E2F, p300, AP1, SP1 and IRF-1/2. Detailed analysis of deletion mutants and elimination of transcr…
Thymoma and paraneoplastic myasthenia gravis
2010
Paraneoplastic autoimmune diseases associate occasionally with small cell lung cancers and gynecologic tumors. However, myasthenia gravis (MG) occurs in at least 30% of all patients with thymomas (usually present at MG diagnosis). These epithelial neoplasms almost always have numerous admixed maturing polyclonal T cells (thymocytes). This thymopoiesis-and export of mature CD4(+)T cells-particularly associates with MG, though there are rare/puzzling exceptions in apparently pure epithelial WHO type A thymomas. Other features potentially leading to inefficient self-tolerance induction include defective epithelial expression of the autoimmune regulator (AIRE) gene and/or of major histocompatib…
Dendritic cell aggresome-like-induced structure formation and delayed antigen presentation coincide in influenza virus-infected dendritic cells.
2005
Abstract Influenza virus infection induces maturation of murine dendritic cells (DCs), which is most important for the initiation of an immune response. However, in contrast to EL-4 and MC57 cells, DCs present viral CTL epitopes with a delay of up to 10 h. This delay in Ag presentation coincides with the up-regulation of MHC class I molecules as well as costimulatory molecules on the cell surface and the accumulation of newly synthesized ubiquitinated proteins in large cytosolic structures, called DC aggresome-like-induced structures (DALIS). These structures were observed previously after LPS-induced maturation of DCs, and it was speculated that they play a role in the regulation of MHC cl…
IAP et Rho : enfin connectées
2014
231 m/s n° 3, vol. 30, mars 2014 DOI : 10.1051/medsci/20143003003 5. Apcher S, Millot G, Daskalogianni C, et al. Translation of pre-spliced RNAs in the nuclear compartment generates peptides for the MHC class I pathway. Proc Natl Acad Sci USA 2013 ; 110 : 17951-6. 6. de Turris V, Nicholson P, Orozco RZ, et al. Cotranscriptional effect of a premature termination codon revealed by live-cell imaging. RNA 2011 ; 17 : 2094-107. 7. Iborra FJ, Jackson DA, Cook PR. Coupled transcription and translation within nuclei of mammalian cells. Science 2001 ; 293 : 1139-42. 8. David A, Dolan BP, Hickman HD, et al. Nuclear translation visualized by ribosome-bound nascent chain puromycylation. J Cell Biol 201…
CD8 T Cells Control Cytomegalovirus Latency by Epitope-Specific Sensing of Transcriptional Reactivation
2006
ABSTRACT During murine cytomegalovirus (mCMV) latency in the lungs, most of the viral genomes are transcriptionally silent at the major immediate-early locus, but rare and stochastic episodes of desilencing lead to the expression of IE1 transcripts. This low-frequency but perpetual expression is accompanied by an activation of lung-resident effector-memory CD8 T cells specific for the antigenic peptide 168-YPHFMPTNL-176, which is derivedfrom the IE1 protein. These molecular and immunological findings were combined in the “silencing/desilencing and immune sensing hypothesis” of cytomegalovirus latency and reactivation. This hypothesis proposes that IE1 gene expression proceeds to cell surfac…
Release of dendritic cells from cognate CD4 + T-cell recognition results in impaired peripheral tolerance and fatal cytotoxic T-cell mediated autoimm…
2012
Resting dendritic cells (DCs) induce tolerance of peripheral T cells that have escaped thymic negative selection and thus contribute significantly to protection against autoimmunity. We recently showed that CD4 + Foxp3 + regulatory T cells (Tregs) are important for maintaining the steady-state phenotype of DCs and their tolerizing capacity in vivo. We now provide evidence that DC activation in the absence of Tregs is a direct consequence of missing DC–Treg interactions rather than being secondary to generalized autoimmunity in Treg-less mice. We show that DCs that lack MHC class II and thus cannot make cognate interactions with CD4 + T cells are completely unable to induce peripheral CD8 +…
Heat shock protein-peptide complexes for use in vaccines
1996
Abstract The heat shock proteins gp96, HSP70, and HSP90 are complexed to a diverse array of cellular proteins and peptides as a consequence of their chaperone functions. There is good experimental evidence that vaccination with these heat shock protein-peptide complexes elicit immune responses against chaperoned peptide antigens. As shown with gp96, this requires internalization of the heat shock protein-peptide complexes by macrophages and processing of the chaperoned peptides for class I restricted presentation. Via this process, primarily CD8+ antigen-specific T cells are primed by gp96 vaccination. This might represent a general mechanism for priming of MHC-class I restricted T cells by…
Distinct bhaplotype structure at the innate immune receptor Toll-like receptor 2 across bank vole populations and lineages in Europe
2015
Abstract: Parasite-mediated selection may contribute to the maintenance of genetic variation at host immune genes over long time scales. To date, the best evidence for the long-term maintenance of immunogenetic variation in natural populations comes from studies on the major histocompatibility complex (MHC) genes, whereas evidence for such processes from other immune genes remains scarce. In the present study, we show that, despite pronounced population differentiation and the occurrence of numerous private alleles within populations, the innate immune gene Toll-like receptor 2 (TLR2) displays a distinct haplotype structure in 21 bank vole (Myodes glareolus) populations across Europe. Haplo…