An adenovirus glycoprotein binds heavy chains of class I transplantation antigens from man and mouse

Nature ◽  
1982 ◽  
Vol 299 (5879) ◽  
pp. 175-178 ◽  
Author(s):  
Christer Signäs ◽  
Michael G. Katze ◽  
Håkan Persson ◽  
Lennart Philipson
Keyword(s):  
Class I ◽  
Heavy Chains ◽  
Transplantation Antigens

scholarly journals Abrogation of cell surface expression of human class I transplantation antigens by an adenovirus protein in Xenopus laevis oocytes.

1985 ◽  
Vol 101 (2) ◽  
pp. 540-547 ◽  
Author(s):  
L Severinsson ◽  
P A Peterson
Keyword(s):  
Cell Surface ◽  
Heavy Chain ◽  
Viral Protein ◽  
Surface Expression ◽  
Class I ◽  
Cell Surface Expression ◽  
Xenopus Laevis Oocytes ◽  
Human Class ◽  
Heavy Chains ◽  
Transplantation Antigens

Class I transplantation antigens form complexes with a virus protein encoded in the early region E3 of the adenovirus-2 genome. The interaction between this viral glycoprotein, E19, and nascent human class I antigens has been examined by microinjecting purified mRNA into Xenopus laevis oocytes. Both E19 and the two class I antigen subunits, the heavy chain and beta 2-microglobulin (beta 2M), were efficiently translated. The heavy chains did not become terminally glycosylated, as monitored by endoglycosidase H digestion, and were not expressed on the oocyte surface unless they were associated with beta 2M. The E19 protein did not become terminally glycosylated, and we failed to detect this viral protein on the surface of the oocytes. Co-translation of heavy chain and E19 mRNA demonstrated that the two proteins associate intracellularly. However, neither protein appeared to be transported to the trans-Golgi compartment. Similar observations were made in adenovirus-infected HeLa cells. Heavy chains bound to beta 2M became terminally glycosylated in oocytes in the presence of low concentrations of E19. At high concentrations of the viral protein, no carbohydrate modifications and no cell surface expression of class I antigens were apparent. Thus, beta 2M and E19 have opposite effects on the intracellular transport of the heavy chains. These data suggest that adenovirus-2 may impede the cell surface expression of class I antigens to escape immune surveillance.

scholarly journals Complex formation of class I transplantation antigens and a viral glycoprotein.

1983 ◽  
Vol 258 (17) ◽  
pp. 10594-10598
Author(s):  
O Kämpe ◽  
D Bellgrau ◽  
U Hammerling ◽  
P Lind ◽  
S Pääbo ◽  
...  
Keyword(s):  
Complex Formation ◽  
Class I ◽  
Viral Glycoprotein ◽  
Transplantation Antigens

scholarly journals The Pathway of Us11-Dependent Degradation of Mhc Class I Heavy Chains Involves a Ubiquitin-Conjugated Intermediate

1999 ◽  
Vol 147 (1) ◽  
pp. 45-58 ◽  
Author(s):  
Caroline E. Shamu ◽  
Craig M. Story ◽  
Tom A. Rapoport ◽  
Hidde L. Ploegh
Keyword(s):  
Mhc Class I ◽  
Heavy Chain ◽  
Control Process ◽  
Degradation Pathway ◽  
Cell System ◽  
Class I ◽  
Permeabilized Cell ◽  
Intact Cells ◽  
Heavy Chains ◽  
Quality Control Process

The human cytomegalovirus protein, US11, initiates the destruction of MHC class I heavy chains by targeting them for dislocation from the ER to the cytosol and subsequent degradation by the proteasome. We report the development of a permeabilized cell system that recapitulates US11-dependent degradation of class I heavy chains. We have used this system, in combination with experiments in intact cells, to identify and order intermediates in the US11-dependent degradation pathway. We find that heavy chains are ubiquitinated before they are degraded. Ubiquitination of the cytosolic tail of heavy chain is not required for its dislocation and degradation, suggesting that ubiquitination occurs after at least part of the heavy chain has been dislocated from the ER. Thus, ubiquitination of the heavy chain does not appear to be the signal to start dislocation. Ubiquitinated heavy chains are associated with membrane fractions, suggesting that ubiquitination occurs while the heavy chain is still bound to the ER membrane. Our results support a model in which US11 co-opts the quality control process by which the cell destroys misfolded ER proteins in order to specifically degrade MHC class I heavy chains.

Molecular definition of soluble HLA class I heavy chains

1993 ◽  
Vol 36 (1) ◽  
pp. 52
Author(s):  
M. Drouet ◽  
L. Aussel ◽  
R. Fauchet
Keyword(s):  
Hla Class I ◽  
Class I ◽  
Heavy Chains ◽  
Soluble Hla ◽  
Definition Of

scholarly journals Distinct Trafficking Pathways Mediate Nef-Induced and Clathrin-Dependent Major Histocompatibility Complex Class I Down-Regulation

2000 ◽  
Vol 74 (19) ◽  
pp. 9256-9266 ◽  
Author(s):  
Sylvie Le Gall ◽  
Florence Buseyne ◽  
Alicja Trocha ◽  
Bruce D. Walker ◽  
Jean-Michel Heard ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Major Histocompatibility Complex Class ◽  
Class I ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Down Regulation ◽  
Class I Mhc ◽  
Mhc I ◽  
Heavy Chains ◽  
Histocompatibility Complex

ABSTRACT The human immunodeficiency virus type 1 Nef protein alters the post-Golgi stages of major histocompatibility complex class I (MHC-I) biogenesis. Presumed mechanisms involve the disclosure of a cryptic tyrosine-based sorting signal (YSQA) located in the cytoplasmic tail of HLA-A and -B heavy chains. We changed this signal for a prototypic sorting motif (YSQI or YSQL). Modified HLA-A2 molecules, termed A2-endo, displayed constitutively low surface levels and accumulated in a region close to or within the Golgi apparatus, a behavior reminiscent of wild-type HLA-A2 in Nef-expressing cells. However, several lines of evidence indicate that the action of prototypic signals on MHC-I trafficking differs from that of Nef. Internalization of surface A2-endo was more rapid and was associated with efficient recycling to the surface. A transdominant-negative mutant of dynamin-1 inhibited A2-endo constitutive internalization and Nef-induced CD4 down-regulation, whereas it did not affect the activity of Nef on MHC-I. Moreover, trafficking of A2-endo was still affected by the viral protein, indicating additive effects of prototypic signals and Nef. Therefore, distinct trafficking pathways regulate clathrin-dependent and Nef-induced MHC-I modulation.

scholarly journals Inhibition of Heavy Chain and β2-Microglobulin Synthesis as a Mechanism of Major Histocompatibility Complex Class I Downregulation during Epstein-Barr Virus Replication

2006 ◽  
Vol 81 (3) ◽  
pp. 1390-1400 ◽  
Author(s):  
Andre Ortlieb Guerreiro-Cacais ◽  
Mehmet Uzunel ◽  
Jelena Levitskaya ◽  
Victor Levitsky
Keyword(s):  
Mhc Class I ◽  
Mhc Class Ii ◽  
Heavy Chain ◽  
Epstein Barr Virus ◽  
Class I ◽  
Heavy Chains ◽  
Barr Virus ◽  
Histocompatibility Complex ◽  
Infected Cells ◽  
Epstein Barr

ABSTRACT The mechanisms of major histocompatibility complex (MHC) class I downregulation during Epstein-Barr virus (EBV) replication are not well characterized. Here we show that in several cell lines infected with a recombinant EBV strain encoding green fluorescent protein (GFP), the virus lytic cycle coincides with GFP expression, which thus can be used as a marker of virus replication. EBV replication resulted in downregulation of MHC class II and all classical MHC class I alleles independently of viral DNA synthesis or late gene expression. Although assembled MHC class I complexes, the total pool of heavy chains, and β2-microglobulin (β2m) were significantly downregulated, free class I heavy chains were stabilized at the surface of cells replicating EBV. Calnexin expression was increased in GFP+ cells, and calnexin and calreticulin accumulated at the cell surface that could contribute to the stabilization of class I heavy chains. Decreased expression levels of another chaperone, ERp57, and TAP2, a transporter associated with antigen processing and presentation, correlated with delayed kinetics of MHC class I maturation. Levels of both class I heavy chain and β2m mRNA were reduced, and metabolic labeling experiments demonstrated a very low rate of class I heavy chain synthesis in lytically infected cells. MHC class I and MHC class II downregulation was mimicked by pharmacological inhibition of protein synthesis in latently infected cells. Our data suggest that although several mechanisms may contribute to MHC class I downregulation in the course of EBV replication, inhibition of MHC class I synthesis plays the primary role in the process.

scholarly journals Endoplasmic reticulum chaperones participate in human cytomegalovirus US2-mediated degradation of class I major histocompatibility complex molecules

2008 ◽  
Vol 89 (5) ◽  
pp. 1122-1130 ◽  
Author(s):  
Kristina Oresic ◽  
Domenico Tortorella
Keyword(s):  
Quality Control ◽  
Endoplasmic Reticulum ◽  
Major Histocompatibility Complex ◽  
Human Cytomegalovirus ◽  
Class I ◽  
Cell Surface Expression ◽  
Major Histocompatibility ◽  
Er Quality Control ◽  
Heavy Chains ◽  
Histocompatibility Complex

Inhibition of cell-surface expression of major histocompatibility complex class I molecules by human cytomegalovirus (HCMV, a β-herpesvirus) promotes escape from recognition by CD8+ cytotoxic T cells. The HCMV US2 and US11 gene products induce class I downregulation during the early phase of HCMV infection by facilitating the degradation of class I heavy chains. The HCMV proteins promote the transport of the class I heavy chains across the endoplasmic reticulum (ER) membrane into the cytosol by a process referred to as ‘dislocation’, which is then followed by proteasome degradation. This process has striking similarities to the degradation of misfolded ER proteins mediated by ER quality control. Even though the major steps of the dislocation reaction have been characterized, the cellular proteins, specifically the ER chaperones involved in targeting class I for dislocation, have not been fully delineated. To elucidate the chaperones involved in HCMV-mediated class I dislocation, we utilized a chimeric class I heavy chain with an affinity tag at its carboxy terminus. Interestingly, US2 but not US11 continued to target the class I chimera for destruction, suggesting a structural limitation for US11-mediated degradation. Association studies in US2 cells and in cells that express a US2 mutant, US2–186HA, revealed that class I specifically interacts with calnexin, BiP and calreticulin. These findings demonstrate that US2-mediated class I destruction utilizes specific chaperones to facilitate class I dislocation. The data suggest a more general model in which the chaperones that mediate protein folding may also function during ER quality control to eliminate aberrant ER proteins.

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