Search results for " present"

Cytomegalovirus Interleukin-10 Expression in Infected Cells Does Not Impair MHC Class I Restricted Peptide Presentation on Bystanding Antigen-Present…

2006

Human cytomegalovirus (HCMV) has evolved strategies to counteract its surveillance by the immune system. Mitigation of antiviral immune responses is considered critical for establishment of viral latency and for spread. Recently, a gene encoding an interleukin-10 homologue (cmvIL-10) has been discovered in the HCMV genome. Using recombinant cmvIL-10, several mostly immunosuppressive functions of the molecule have been described. However, the role of cmvIL-10 in the context of viral infection was not addressed. To be able to analyze this issue, we generated cmvIL- 10-negative viral mutants. Using these mutants, we tested whether the expression of cmvIL-10 by infected cells would render bysta…

H2-Mβ1 and H2-Mβ2 Heterodimers Equally Promote CLIP Removal in I-Aq Molecules from Autoimmune-prone DBA/1 Mice

2001

Antigen-presenting cells degrade endocytosed antigens, e.g. collagen type II, into peptides that are bound and presented to arthritogenic CD4(+) helper T cells by major histocompatibility complex (MHC) class II molecules. Efficient loading of many MHC class II alleles with peptides requires the assistance of H2-M (HLA-DM in humans), a heterodimeric MHC class II-like molecule that facilitates CLIP removal from MHC class II molecules and aids to shape the peptide repertoire presented by MHC class II to CD4(+) T cells. In contrast to the HLA-DM region in humans, the beta-chain locus is duplicated in mice, with the H2-Mb1 beta-chain distal to H2-Mb2 and the H2-Ma alpha-chain gene. H2-M alleles …

2013

The MHC-class I (MHC-I)-like viral (MHC-Iv) m152 gene product of murine cytomegalovirus (mCMV) was the first immune evasion molecule described for a member of the β-subfamily of herpesviruses as a paradigm for analogous functions of human cytomegalovirus proteins. Notably, by interacting with classical MHC-I molecules and with MHC-I-like RAE1 family ligands of the activatory natural killer (NK) cell receptor NKG2D, it inhibits presentation of antigenic peptides to CD8 T cells and the NKG2D-dependent activation of NK cells, respectively, thus simultaneously interfering with adaptive and innate immune recognition of infected cells. Although the m152 gene product exists in differentially glyco…

Human cytomegalovirus US3 modulates destruction of MHC class I molecules

2012

Human cytomegalovirus (HCMV), a member of the Herpesviridae family, is proficient at establishing lifelong persistence within the host in part due to immune modulating genes that limit immune recognition. HCMV encodes at least five glycoproteins within its unique short (US) genomic region that interfere with MHC class I antigen presentation, thus hindering viral clearance by cytotoxic T lymphocytes (CTL). Specifically, US3 retains class I within the endoplasmic reticulum (ER), while US2 and US11 induce class I heavy chain destruction. A cooperative effect on class I down-regulation during stable expression of HCMV US2 and US3 has been established. To address the impact of US3 on US11-mediat…

Identification of sequences in the human peptide transporter subunit TAP1 required for transporter associated with antigen processing (TAP) function

2001

The heterodimeric peptide transporter associated with antigen processing (TAP) consisting of the subunits TAP1 and TAP2 mediates the transport of cytosolic peptides into the lumen of the endoplasmic reticulum (ER). In order to accurately define domains required for peptide transporter function, a molecular approach based on the construction of a panel of human TAP1 mutants and their expression in TAP1(-/-) cells was employed. The characteristics and biological activity of the various TAP1 mutants were determined, and compared to that of wild-type TAP1 and TAP1(-/-) control cells. All mutant TAP1 proteins were localized in the ER and were capable of forming complexes with the TAP2 subunit. H…

A high-throughput genome-wide siRNA screen for ciliogenesis identifies new ciliary functional components and ciliopathy genes.

2015

Defects in primary cilium biogenesis underlie the ciliopathies, a growing group of genetic disorders. We describe the first whole genome siRNA-based reverse genetics screen for defects in biogenesis and/or maintenance of the primary cilium, obtaining a global resource for investigation and interventions into the processes that are critical for the ciliary system. In total, we identified 83 candidate ciliogenesis and ciliopathy genes, including 15 components of the ubiquitin-proteasome system. The validated hits also include 12 encoding G-protein-coupled receptors, and three encoding pre-mRNA processing factors (PRPF6, PRPF8 and PRPF31) mutated in autosomal dominant retinitis pigmentosa. Com…

Major Histocompatibility Complex Polymorphisms and Ageing.

2004

ASTRACT Longevity seems to be directly correlated with optimal functioning of the immune system, suggesting that some genetic determinants of longevity might reside in those polymorphisms for the immune system genes that regulate immune responses. Accordingly, mouse lifespan is influenced by MHC (major histocompatibility complex) genotype. The HLA (the human MHC) region encompasses over 4 Mb of DNA on the chromosome band 6p21.3 and its extensive characterisation has recently culminated in the determination of the nucleotide sequence of the entire region, confirming the presence of ~ 220 genes. The MHC is traditionally divided into the class I, class II and class III regions. Most HLA genes …

Transgenic tools for proteomic analysis of ciliary transport

2015

Vision begins as photons are captured by photoreceptor cilia and light is converted into electrical signals that are then sent to the brain. As the photoreceptor cilium is not able to make its own proteins, all polypeptides needed for converting photons into electrical signals are synthetized in the cell body. How these molecules move from the cell body to cilia is still unclear. Opsin is one of the best-characterized transmembrane proteins. Our goal is to understand the mechanism of opsin transport into photoreceptor cilia. In this project, we use a combination of genetic and proteomic approaches in the zebrafish model. As the first step, we are constructing a transgenic line that expresse…

Identification of novel interaction partners for Vlgr1b/GPR98 - a key component of the periciliary Usher syndrome protein network in photoreceptor ce…

2012

The human Usher syndrome (USH) is the most common form of combined hereditary deaf-blindness. Three clinical subtypes (USH1-3) are differentiated based on severity, age of onset and progression of the symptoms. Mutations in the GPR98 gene encoding the USH2C protein Vlgr1b or GPR98 cause USH2, the most common form of USH. The G-protein coupled receptor Vlgr1b was previously identified as a component of the periciliary USH protein network, crucial for ciliary cargo transport in photoreceptors. Nonetheless, the exact role of Vlgr1b in this and other cellular processes remains to be elucidated. To learn more about its involvement in cellular functions we searched for novel interaction partners …

Nanodiamond-Rich Layer across Three Continents Consistent with Major Cosmic Impact at 12,800 Cal BP

2014

© 2014 by The University of Chicago. All rights reserved. A major cosmic-impact event has been proposed at the onset of the Younger Dryas (YD) cooling episode at ≈12,800 ± 150 years before present, forming the YD Boundary (YDB) layer, distributed over 150 million km2 on four continents. In 24 dated stratigraphic sections in 10 countries of the Northern Hemisphere, the YDB layer contains a clearly defined abundance peak in nanodiamonds (NDs), a major cosmic-impact proxy. Observed ND polytypes include cubic diamonds, lonsdaleite-like crystals, and diamond-like carbon nanoparticles, called n-diamond and i-carbon. The ND abundances in bulk YDB sediments ranged up to ≈500 ppb (mean: 200 ppb) and…