scholarly journals Major Histocompatibility Complex Class I Allele-specific Cooperative and Competitive Interactions between Immune Evasion Proteins of Cytomegalovirus

2002 ◽  
Vol 196 (6) ◽  
pp. 805-816 ◽  
Author(s):  
Markus Wagner ◽  
Anja Gutermann ◽  
Jürgen Podlech ◽  
Matthias J. Reddehase ◽  
Ulrich H. Koszinowski
Keyword(s):  
Major Histocompatibility Complex ◽  
Mhc Class I ◽  
Surface Expression ◽  
Inhibitory Effect ◽  
Class I ◽  
Major Influence ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Allele Specific ◽  
Infected Cells

Cytomegaloviruses (CMVs) deploy a set of genes for interference with antigen presentation in the major histocompatibility complex (MHC) class I pathway. In murine CMV (MCMV), three genes were identified so far: m04/gp34, m06/gp48, and m152/gp40. While their function as immunoevasins was originally defined after their selective expression, this may not necessarily reflect their biological role during infection. The three immunoevasins might act synergistically, but they might also compete for their common substrate, the MHC class I complexes. To approach this question in a systematic manner, we have generated a complete set of mutant viruses with deletions of the three genes in all seven possible combinations. Surface expression of a set of MHC class I molecules specified by haplotypes H-2d (Kd, Dd, and Ld) and H-2b (Kb and Db) was the parameter for evaluation of the interference with class I trafficking. The data show the following: first, there exists no additional MCMV gene of major influence on MHC class I surface expression; second, the strength of the inhibitory effect of immunoevasins shows an allele-specific hierarchy; and third, the immunoevasins act not only synergistically but can, in certain combinations, interact antagonistically. In essence, this work highlights the importance of studying the immunosubversive mechanisms of cytomegaloviruses in the context of gene expression during the viral replicative cycle in infected cells.

scholarly journals E3/19K from adenovirus 2 is an immunosubversive protein that binds to a structural motif regulating the intracellular transport of major histocompatibility complex class I proteins.

1990 ◽  
Vol 172 (6) ◽  
pp. 1653-1664 ◽  
Author(s):  
W A Jefferies ◽  
H G Burgert
Keyword(s):  
Major Histocompatibility Complex ◽  
Cell Surface ◽  
Mhc Class I ◽  
Intracellular Transport ◽  
Surface Expression ◽  
Class I ◽  
Cell Surface Expression ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Mhc Class I Molecules

We have previously expressed in transgenic mice a chimeric H-2Kd/Kk protein called C31, which contains the extracellular alpha 1 domain of Kd, whereas the rest of the molecule is of Kk origin. This molecule functions as a restriction element for alloreactive and influenza A-specific cytotoxic T lymphocytes (CTL) but is only weakly expressed at the cell surface of splenocytes. Here, we show that the low cell surface expression is the result of slow intracellular transport and processing of the C31 protein. A set of hybrid molecules between Kd and Kk were used to localize the regions in major histocompatibility complex (MHC) molecules that are important for their intracellular transport and to further localize the structures responsible for binding to the adenovirus 2 E3/19K protein. This protein appears to be an important mediator of adenovirus persistence. It acts by binding to the immaturely glycosylated forms of MHC class I proteins in the endoplasmic reticulum (ER), preventing their passage to the cell surface and thereby reducing the recognition of infected cells by virus-specific T cells. We find the surprising result that intracellular transport and E3/19K binding are controlled primarily by the first half of the second domain of Kd, thus localizing these phenomena to the five polymorphic residues in this region of the Kd protein. This result implies that the E3/19K protein may act by inhibiting peptide binding or by disrupting the oligomerization of MHC class I molecules required for transport out of the ER. Alternatively, the E3/19K protein may inhibit the function of a positively acting transport molecule necessary for cell surface expression of MHC class I molecules.

scholarly journals Degradation of Transcription Factor Rfx5 during the Inhibition of Both Constitutive and Interferon γ–Inducible Major Histocompatibility Complex Class I Expression in Chlamydia-Infected Cells

2000 ◽  
Vol 191 (9) ◽  
pp. 1525-1534 ◽  
Author(s):  
Guangming Zhong ◽  
Li Liu ◽  
Tao Fan ◽  
Peiyi Fan ◽  
Hezhao Ji
Keyword(s):  
Transcription Factor ◽  
Major Histocompatibility Complex ◽  
Mhc Class I ◽  
Host Protein ◽  
Class I ◽  
Immune Recognition ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Infected Cells ◽  
Ifn Γ

We have previously shown that the obligate intracellular pathogen chlamydia can suppress interferon (IFN)-γ–inducible major histocompatibility complex (MHC) class II expression in infected cells by degrading upstream stimulation factor (USF)-1. We now report that chlamydia can also inhibit both constitutive and IFN-γ–inducible MHC class I expression in the infected cells. The inhibition of MHC class I molecule expression correlates well with degradation of RFX5, an essential downstream transcription factor required for both the constitutive and IFN-γ–inducible MHC class I expression. We further demonstrate that a lactacystin-sensitive proteasome-like activity identified in chlamydia-infected cell cytosolic fraction can degrade both USF-1 and RFX5. This proteasome-like activity is dependent on chlamydial but not host protein synthesis. Host preexisting proteasomes may not be required for the unique proteasome-like activity. These observations suggest that chlamydia-secreted factors may directly participate in the proteasome-like activity. Efforts to identify the chlamydial factors are underway. These findings provide novel information on the molecular mechanisms of chlamydial evasion of host immune recognition.

scholarly journals Macrophages Escape Inhibition of Major Histocompatibility Complex Class I-Dependent Antigen Presentation by Cytomegalovirus

2000 ◽  
Vol 74 (17) ◽  
pp. 7861-7868 ◽  
Author(s):  
Hartmut Hengel ◽  
Uwe Reusch ◽  
Gernot Geginat ◽  
Rafaela Holtappels ◽  
Thomas Ruppert ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Major Histocompatibility Complex ◽  
Antigen Presentation ◽  
Mhc Class I ◽  
Surface Expression ◽  
Class I ◽  
Major Histocompatibility ◽  
Mcmv Infection ◽  
Early Protein ◽  
Histocompatibility Complex

ABSTRACT The mouse cytomegalovirus (MCMV) m152- andm06-encoded glycoproteins gp40 and gp48, respectively, independently downregulate major histocompatibility complex (MHC) class I surface expression during the course of productive MCMV infection in fibroblasts. As a result, presentation of an immediate-early protein pp89-derived nonapeptide to H-2Ld -restricted CD8+ cytotoxic T cells is completely prevented in fibroblasts. Here we demonstrate that MCMV-infected primary bone marrow macrophages and the macrophage cell line J774 constitutively present pp89 peptides during permissive MCMV infection to cytotoxic T lymphocytes (CTL). In contrast to fibroblasts, expression of them152 and m06 genes in macrophages does not affect surface expression of MHC class I. Assessment of pp89 synthesis and quantification of extracted peptide revealed a significantly higher efficiency of macrophages than of fibroblasts to process pp89 into finally trimmed peptide. The yield of pp89 peptide determined in MCMV-infected tissues of bone marrow chimeras confirmed that bone marrow-derived cells represent a prime source of pp89 processing in parenchymal organs. The finding that macrophages resist the viral control of MHC I-dependent antigen presentation reconciles the paradox of efficient induction of CMV-specific CD8+ CTL in vivo despite extensive potential of CMVs to subvert MHC class I.

Transcription of non-classic major histocompatibility complex (MHC) class I in the bovine placenta throughout gestation and after Brucella abortus infection

2015 ◽  
Vol 167 (3-4) ◽  
pp. 166-170
Author(s):  
Larissa Sarmento dos Santos ◽  
Juliana Pinto da Silva Mol ◽  
Auricélio Alves de Macedo ◽  
Ana Patrícia Carvalho Silva ◽  
Diego Luiz dos Santos Ribeiro ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Mhc Class I ◽  
Brucella Abortus ◽  
Class I ◽  
Major Histocompatibility ◽  
Bovine Placenta ◽  
Histocompatibility Complex

scholarly journals Major histocompatibility complex class I molecules mediate association of SV40 with caveolae.

1997 ◽  
Vol 8 (1) ◽  
pp. 47-57 ◽  
Author(s):  
E Stang ◽  
J Kartenbeck ◽  
R G Parton
Keyword(s):  
Major Histocompatibility Complex ◽  
Mhc Class I ◽  
Mammalian Cells ◽  
Simian Virus 40 ◽  
Class I ◽  
Major Histocompatibility ◽  
Surface Binding ◽  
Histocompatibility Complex ◽  
Mhc Class I Molecule ◽  
Mhc Class I Molecules

Simian virus 40 (SV40) has been shown to enter mammalian cells via uncoated plasma membrane invaginations. Viral particles subsequently appear within the endoplasmic reticulum. In the present study, we have examined the surface binding and internalization of SV40 by immunoelectron microscopy. We show that SV40 associates with surface pits which have the characteristics of caveolae and are labeled with antibodies to the caveolar marker protein, caveolin-1. SV40 is believed to use major histocompatibility complex (MHC) class I molecules as cell surface receptors. Using a number of MHC class I-specific monoclonal antibodies, we found that both viral infection and association of virus with caveolae were strongly reduced by preincubation with anti-MHC class I antibodies. Because binding of SV40 to MHC class I molecules may induce clustering, we investigated whether antibody cross-linked class I molecules also redistributed to caveolae. Clusters of MHC class I molecules were indeed shown to be specifically associated with caveolin-labeled surface pits. Taken together, the results suggest that SV40 may make use of MHC class I molecule clustering and the caveolae pathway to enter mammalian cells.

Nonimmune thyroid destruction results from transgenic overexpression of an allogeneic major histocompatibility complex class I protein

1993 ◽  
Vol 13 (3) ◽  
pp. 1554-1564
Author(s):  
A G Frauman ◽  
P Chu ◽  
L C Harrison
Keyword(s):  
Major Histocompatibility Complex ◽  
Beta Cells ◽  
Mhc Class I ◽  
Pancreatic Beta Cells ◽  
Class I ◽  
General Mechanism ◽  
Major Histocompatibility ◽  
Cell Destruction ◽  
Histocompatibility Complex ◽  
Mhc Class I Molecules

The overexpression of major histocompatibility complex (MHC) class I molecules in endocrine epithelial cells is an early feature of autoimmune thyroid disease and insulin-dependent diabetes mellitus, which may reflect a cellular response, e.g., to viruses or toxins. Evidence from a transgenic model in pancreatic beta cells suggests that MHC class I overexpression could play an independent role in endocrine cell destruction. We demonstrate in this study that the transgenic overexpression of an allogeneic MHC class I protein (H-2Kb) linked to the rat thyroglobulin promoter, in H-2Kk mice homozygous for the transgene, leads to thyrocyte atrophy, hypothyroidism, growth retardation, and death. Thyrocyte atrophy occurred in the absence of lymphocytic infiltration. Tolerance to allogeneic class I was revealed by the reduced ability of primed lymphocytes from transgenic mice to lyse H-2Kb target cells in vitro. This nonimmune form of thyrocyte destruction and hypothyroidism recapitulates the beta-cell destruction and diabetes that results from transgenic overexpression of MHC class I molecules in pancreatic beta cells. Thus, we conclude that overexpression of MHC class I molecules may be a general mechanism that directly impairs endocrine epithelial cell viability.

scholarly journals A Human Herpesvirus 7 Glycoprotein, U21, Diverts Major Histocompatibility Complex Class I Molecules to Lysosomes

2001 ◽  
Vol 75 (24) ◽  
pp. 12347-12358 ◽  
Author(s):  
Amy W. Hudson ◽  
Peter M. Howley ◽  
Hidde L. Ploegh
Keyword(s):  
Major Histocompatibility Complex ◽  
Major Histocompatibility Complex Class ◽  
Cytotoxic T Lymphocytes ◽  
Human Herpesvirus ◽  
Class I ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Infected Cells ◽  
Immune Detection

ABSTRACT All members of the herpesvirus family persist in their host throughout life. In doing so, herpesviruses exploit a surprising number of different strategies to evade the immune system. Human herpesvirus 7 (HHV-7) is a relatively recently discovered member of the herpesvirus family, and little is known about how it escapes immune detection. Here we show that HHV-7 infection results in premature degradation of major histocompatibility complex class I molecules. We identify and characterize a protein from HHV-7, U21, that binds to and diverts properly folded class I molecules to a lysosomal compartment. Thus, U21 is likely to function in the normal course of HHV-7 infection to downregulate surface class I molecules and prevent recognition of infected cells by cytotoxic T lymphocytes.

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