Traffic control of completely assembled MHC class I molecules beyond the endoplasmic reticulum

Joyce, Sebastian

doi:10.1006/jmbi.1996.0822

Cited by 28 publications

(18 citation statements)

References 28 publications

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“…However, recent study by Joyce (11) showed that the surface expression of MHC class I molecules was not up-regulated in the MHC class I over-expressing cell lines without defects of transport from the ER to the Golgi, suggesting that the expression of MHC class I molecules at the cell surfaces could be regulated by internalization and recycling or sorting in the trans-Golgi or TGN. According to several recent reports, HIV-1 Nef uses both mechanisms, acceleration of their endocytosis and accumulation in the Golgi (16, 27, 36) for the down-regulation of cell surface expression of MHC class I molecules.…”

Section: Discussionmentioning

confidence: 95%

“…Upon leaving the ER, MHC class I molecules have been generally known to rapidly arrive at the cell surface by default pathway without requirements for specific signals (bulk flow) (10). However, recent evidence of sorting of MHC class I molecules in the TGN suggests that the regulated expression of MHC class I molecules at the cell surface can be achieved through the post-Golgi traffic control (11).…”

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confidence: 99%

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CD99 Regulates the Transport of MHC Class I Molecules from the Golgi Complex to the Cell Surface

Sohn¹,

Shin²,

Lee

et al. 2001

The Journal of Immunology

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The down-regulation of surface expression of MHC class I molecules has recently been reported in the CD99-deficient lymphoblastoid B cell line displaying the characteristics of Hodgkin’s and Reed-Sternberg phenotype. Here, we demonstrate that the reduction of MHC class I molecules on the cell surface is primarily due to a defect in the transport from the Golgi complex to the plasma membrane. Loss of CD99 did not affect the steady-state expression levels of mRNA and protein of MHC class I molecules. In addition, the assembly of MHC class I molecules and the transport from the endoplasmic reticulum to the cis-Golgi occurred normally in the CD99-deficient cells, and no difference was detected between the CD99-deficient and the control cells in the pattern and degree of endocytosis. Instead, the CD99-deficient cells displayed the delayed transport of newly synthesized MHC class I molecules to the plasma membrane, thus causing accumulation of the molecules within the cells. The accumulated MHC class I molecules in the CD99-deficient cells were colocalized with α-mannosidase II and γ-adaptin in the Golgi compartment. These results suggest that CD99 may be associated with the post-Golgi trafficking machinery by regulating the transport to the plasma membrane rather than the endocytosis of surface MHC class I molecules, providing a novel mechanism of MHC class I down-regulation for immune escape.

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Section: Discussionmentioning

confidence: 95%

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confidence: 99%

CD99 Regulates the Transport of MHC Class I Molecules from the Golgi Complex to the Cell Surface

Sohn¹,

Shin²,

Lee

et al. 2001

The Journal of Immunology

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“…For immunofluorescence, we used W6/32 (Barnstable et al, 1978), which recognizes HLA-A, HLA-B, and HLA-C. When used on HLA-A2-expressing HeLa cells, all of the above-mentioned antibodies exclusively or primarily recognized HLA-A2, because it has been shown that expression of other MHC-I isotypes is greatly reduced when a particular isotype is overexpressed (Joyce, 1997). For flow cytometry on the parental HeLa cell line, which expresses HLA-A6802/B1503/C1203 (Peter Cresswell, personal communication), we used W6/32 (see above) and 4E (Yang et al, 1984;Zinszner et al, 1990), which binds HLA-B and HLA-C.…”

Section: Antibodiesmentioning

confidence: 99%

“…For technical reasons, the cells were not labeled with the HLA-A2-specific antibody that we used for flow cytometry, but with an antibody that recognizes all human MHC-I isotypes; however, there is evidence that HLA-A2 is the major MHC-I isotype expressed in these cells (Joyce, 1997). The cells were fixed with paraformaldehyde and labeled for surface MHC-I, and then they were permeabilized with Triton X-100 and labeled again with the same primary antibody followed by a different secondary antibody to visualize total MHC-I.…”

Section: Localization and Turnover Of Mhc Class I In Nef-expressing Cmentioning

confidence: 99%

HIV-1 Nef-induced Down-Regulation of MHC Class I Requires AP-1 and Clathrin but Not PACS-1 and Is Impeded by AP-2

Lubben

Sahlender

Motley

et al. 2007

MBoC

106

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Major histocompatibility complex class I is down-regulated from the surface of human immunodeficiency virus (HIV)-1-infected cells by Nef, a virally encoded protein that is thought to reroute MHC-I to the trans-Golgi network (TGN) in a phosphofurin acidic cluster sorting protein (PACS) 1, adaptor protein (AP)-1, and clathrin-dependent manner. More recently, an alternative model has been proposed, in which Nef uses AP-1 to direct MHC-I to endosomes and lysosomes. Here, we show that knocking down either AP-1 or clathrin with small interfering RNA inhibits the down-regulation of HLA-A2 (an MHC-I isotype) by Nef in HeLa cells. However, knocking down PACS-1 has no effect, not only on Nef-induced down-regulation of HLA-A2 but also on the localization of other proteins containing acidic cluster motifs. Surprisingly, knocking down AP-2 actually enhances Nef activity. Immuno-electron microscopy labeling of Nef-expressing cells indicates that HLA-A2 is rerouted not to the TGN, but to endosomes. In AP-2-depleted cells, more of the HLA-A2 localizes to the inner vesicles of multivesicular bodies. We propose that depleting AP-2 potentiates Nef activity by altering the membrane composition and dynamics of endosomes and causing increased delivery of HLA-A2 to a prelysosomal compartment. INTRODUCTIONLike many viruses, human immunodeficiency virus (HIV)-1 has evolved strategies to avoid detection and destruction by the host. One such strategy is the down-regulation of major histocompatability complex (MHC) class I from the plasma membrane of HIV-1-infected cells, which prevents the cells from being attacked by cytotoxic T lymphocytes. MHC-I down-regulation has been shown to be a function of a virally encoded protein called Nef (Schwartz et al., 1996;Collins et al., 1998). Nef is one of the so-called "accessory proteins" of both human and simian immunodeficiency viruses: although not required for viral replication in vitro, Nef plays a key role in the development of acquired immunodeficiency syndrome. Nef is a small protein, only ϳ200 amino acids, but it has been reported to interact with a large number of host cell proteins, including several proteins that are involved in membrane traffic. These interactions are thought to be responsible for the ability of Nef to modulate the surface expression of MHC-I and other molecules (for review, see Collins and Baltimore, 1999;Piguet et al., 1999;Doms and Trono, 2000;Roeth and Collins, 2006).Among the binding partners that have been identified for Nef are the adaptor protein (AP) complexes. There are four AP complexes in mammalian cells, two of which, AP-1 and AP-2, are highly enriched in clathrin-coated vesicles (CCVs). AP-1 facilitates clathrin-mediated trafficking between the trans-Golgi network (TGN) and endosomes (although there is still some question about directionality), and AP-2 facilitates clathrin-mediated endocytosis (Robinson, 2004). AP-3, which seems to be able to act both in a clathrin-dependent and in a clathrin-independent manner (Dell'Angelica et al., 1998;Peden et al., 2...

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“…NS0, a H2 d plasmacytoma, was maintained in DMEM (Life Technologies) supplemented with FCS, penicillin, streptomycin, and L-glutamine. Kb-high NS0 transfected with full length H2K b cDNA was maintained in L-glutamine-deficient DMEM (Life Technologies) supplemented with 5-10% dialyzed FCS (HyClone), penicillin, streptomycin, essential amino acids, and nucleosides as described (23).…”

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confidence: 99%

The H4b Minor Histocompatibility Antigen Is Caused by a Combination of Genetically Determined and Posttranslational Modifications

Yadav

Yoshimura

Boesteanu

et al. 2003

The Journal of Immunology

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Minor histocompatibility (H) Ag disparities result in graft-vs-host disease and chronic solid allograft rejection in MHC-identical donor-recipient combinations. Minor H Ags are self protein-derived peptides presented by MHC class I molecules. Most arise as a consequence of allelic variation in the bound peptide (p) that results in TCR recognizing the p/MHC as foreign. We used a combinational peptide screening approach to identify the immune dominant H2Kb-restricted epitope defining the mouse H4b minor H Ag. H4b is a consequence of a P3 threonine to isoleucine change in the MHC-bound peptide derived from epithelial membrane protein-3. This allelic variation also leads to phosphorylation of the H4b but not the H4a epitope. Further, ex vivo CD8+ T lymphocytes bind phosphorylated Ag tetramers with high efficiency. Although we document the above process in the minor H Ag system, posttranslational modifications made possible by subtle amino acid changes could also contribute to immunogenicity and immune dominance in tumor immunotherapeutic settings.

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Traffic control of completely assembled MHC class I molecules beyond the endoplasmic reticulum

Cited by 28 publications

References 28 publications

CD99 Regulates the Transport of MHC Class I Molecules from the Golgi Complex to the Cell Surface

CD99 Regulates the Transport of MHC Class I Molecules from the Golgi Complex to the Cell Surface

HIV-1 Nef-induced Down-Regulation of MHC Class I Requires AP-1 and Clathrin but Not PACS-1 and Is Impeded by AP-2

The H4b Minor Histocompatibility Antigen Is Caused by a Combination of Genetically Determined and Posttranslational Modifications

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