Human cytomegalovirus US3 impairs transport and maturation of major histocompatibility complex class I heavy chains.

Jones, Thomas R.; Wiertz, Emmanuel J. H. J.; Sun, Lei; Fish, Kenneth N.; Nelson, Jay A.; Ploegh, Hidde L.

doi:10.1073/pnas.93.21.11327

Cited by 378 publications

(333 citation statements)

References 41 publications

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“…Although the hCMV US gene products US2, 3, 6, and 11 can reduce the MHC class I antigen expression level on the cell surface after a viral infection by various mechanisms [22][23][24][25][26], it is not known if US gene transfection affects the MHC class I expression on stem cells. Therefore, this study tested MHC class I expression on US genetransfected HB1.F3 cells or mock-transfected cells 48 h after the IFN-c treatment using immunofluorescence analysis.…”

Section: Modification Of Mhc Class I Expression Of Hb1f3 Cells With mentioning

confidence: 99%

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Down-regulation of MHC class I expression in human neuronal stem cells using viral stealth mechanism

Lee

Kim

Cho

et al. 2005

Biochemical and Biophysical Research Communications

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Section: Modification Of Mhc Class I Expression Of Hb1f3 Cells With mentioning

confidence: 99%

“…Its gene products, US2, US3, US6, and US11, can independently reduce MHC class I expression on the cell surface [22][23][24][25][26].…”

mentioning

confidence: 99%

Down-regulation of MHC class I expression in human neuronal stem cells using viral stealth mechanism

Lee

Kim

Cho

et al. 2005

Biochemical and Biophysical Research Communications

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“…3A). Although the identity of this protein is unknown, its size is consistent with the molecular masses of class I heavy chains from other species (Campbell & Slater, 1994;Jones & Sun, 1997) and therefore it is possible that this protein is the guinea pig class I heavy chain.…”

mentioning

confidence: 70%

“…These strains express a number of proteins designed to modify host immune responses, including four that down-regulate surface expression of MHC class I (Ahn et al, 1997;Jones et al, 1995Jones et al, , 1996Jones & Sun, 1997;Wiertz et al, 1996). As antigen presentation by class I is critical for induction of both cell-and antibody-mediated host immunity, down-regulation of class I by vaccine strains is counter-intuitive to induction of robust immune responses.…”

mentioning

confidence: 99%

Down-regulation of surface major histocompatibility complex class I by guinea pig cytomegalovirus

Lacayo

Sato

Kamiya

et al. 2003

Journal of General Virology

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“…Finally, the importance of the dissociation of the tapasin-ERp57 conjugate in regulating the release of MHC class I molecules is further emphasized by studies indicating that human cytomegalovirus has evolved to specifically target the tapasin-ERp57 conjugate for immune evasion. The human cytomegalovirus US3 glycoprotein inhibits the transport of MHC class I molecules from the ER (Ahn et al, 1996;Jones et al, 1996). Recently, the US3 protein has been shown to target the degradation of PDI for CD8 ϩ T-cell evasion (Park et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Redox-regulated Export of the Major Histocompatibility Complex Class I-Peptide Complexes from the Endoplasmic Reticulum

Lee

Park

Kang

et al. 2009

MBoC

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In contrast to the fairly well-characterized mechanism of assembly of MHC class I-peptide complexes, the disassembly mechanism by which peptide-loaded MHC class I molecules are released from the peptide-loading complex and exit the endoplasmic reticulum (ER) is poorly understood. Optimal peptide binding by MHC class I molecules is assumed to be sufficient for triggering exit of peptide-filled MHC class I molecules from the ER. We now show that protein disulfide isomerase (PDI) controls MHC class I disassembly by regulating dissociation of the tapasin-ERp57 disulfide conjugate. PDI acts as a peptide-dependent molecular switch; in the peptide-bound state, it binds to tapasin and ERp57 and induces dissociation of the tapasin-ERp57 conjugate. In the peptide-free state, PDI is incompetent to bind to tapasin or ERp57 and fails to dissociate the tapasin-ERp57 conjugates, resulting in ER retention of MHC class I molecules. Thus, our results indicate that even after optimal peptide loading, MHC class I disassembly does not occur by default but, rather, is a regulated process involving PDI-mediated interactions within the peptide-loading complex. INTRODUCTIONAssembly of major histocompatibility complex (MHC) class I molecules within the endoplasmic reticulum (ER) is essential for bringing antigenic peptides to CD8 ϩ T-cells, which scan and destroy the infected and transformed cells. MHC class I quality control ensures both the ER retention of suboptimally loaded MHC class I molecules and the release of those with a higher affinity to the cell surface. Therefore, the peptide-editing process for optimal peptide loading is critical for increasing the recognition by CD8 ϩ T-cells (Van Kaer, 2002;Cresswell, 2005).MHC class I assembly is a highly regulated process mediated by several ER-resident chaperones and accessory molecules (Cresswell, 2000;Williams et al., 2002a). After initial interaction with the lectin-like chaperone calnexin, MHC class I heavy chain-␤ 2 -microglobulin (␤ 2 m) heterodimers are incorporated into the peptide-loading complex (PLC), a multimolecular unit of ER proteins that promotes optimal peptide loading into MHC class I molecules (Hammerling et al., 1998;Pamer and Cresswell, 1998;Elliott and Williams, 2005). The PLC contains calreticulin, tapasin, transporters associated with antigen processing (TAP) and two thioldependent oxidoreductases, ERp57 and protein disulfide isomerase (PDI) (Garbi et al., 2005;Park et al., 2006;Santos et al., 2007).Several functions have been proposed for tapasin in facilitating optimal peptide loading and optimization of the peptide cargo (Grandea and Van Kaer, 2001;Purcell et al., 2001;Momburg and Tan, 2002). Tapasin bridges heavy chain-␤ 2 m heterodimers to TAP (Sadasivan et al., 1996) and thus provides physical proximity between MHC class I molecules and TAP. Tapasin also retains MHC class I molecules in the ER (Schoenhals et al., 1999;Barnden et al., 2000;Grandea et al., 2000), which might enhance peptide loading. In addition, tapasin optimizes the repertoire of bound pep...

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Human cytomegalovirus US3 impairs transport and maturation of major histocompatibility complex class I heavy chains.

Cited by 378 publications

References 41 publications

Down-regulation of MHC class I expression in human neuronal stem cells using viral stealth mechanism

Down-regulation of MHC class I expression in human neuronal stem cells using viral stealth mechanism

Down-regulation of surface major histocompatibility complex class I by guinea pig cytomegalovirus

Redox-regulated Export of the Major Histocompatibility Complex Class I-Peptide Complexes from the Endoplasmic Reticulum

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