Segregation of MHC class II molecules from MHC class I molecules in the Golgi complex for transport to lysosomal compartments

Peters, Peter J.; Neefjes, Jacques; Oorschot, Viola; Ploegh, Hidde L.; Geuze, Hans J.

doi:10.1038/349669a0

Cited by 620 publications

(460 citation statements)

References 43 publications

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“…The invariant chain (Ii) is required for assembly of class II molecules (Anderson and Miller, 1992;Peterson and Miller, 1990), and transport of the class II heterodimer to the appropriate endosomal compartment (the MIIC) (Bakke and Dobberstein, 1990;Lamb and Cresswell, 1992;Lotteau et al, 1990;Neefjes et al, 1990;Peters et al, 1991). An Ii proteolytic fragment, the class IIassociated Ii peptide (CLIP), occupies the peptide binding site until it is subsequently replaced by antigenic peptides in the MIIC.…”

Section: Ifn-g-induction Of II and H2-m Is Prb-independentmentioning

confidence: 99%

pRB is required for interferon-γ-induction of the MHC class II Aβ gene

Zhu¹,

Pattenden

Bremner

1999

Oncogene

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pRB is required for IFN-g-induction of MHC class II in human tumor cell lines, providing a potential link between tumor suppressors and the immune system. However, other genes, such as cyclin D1, show pRBdependency only in tumor cells, so by analogy, pRB may not be necessary for cII-regulation in normal cells. Here, we demonstrate that induction of the mouse MHC class II I-A heterodimer is normal in RB +/+ mouse embryonic ®broblasts (MEFs), but de®cient in RB 7/7 MEFs. Inducibility is restored in RB 7/7 MEFs stably transfected with wild type RB cDNA or infected with an adenovirus expressing pRB. Thus, involvement of pRB in MHC class II expression is conserved in the mouse and is not an aberrant feature of tumorigenic, aneuploid, human tumor cells. Although cII genes are generally induced in a coordinate fashion, suggesting a common mechanism, we found that pRB was speci®cally required for induction of the Ab, but not Aa or other MHC cII genes including Eb, Ii and H2-Ma. Finally, IFN-ginduction of class II transactivator (CIITA), was pRBindependent, suggesting that pRB works downstream of this master-regulator of MHC class II expression.

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Section: Ifn-g-induction Of II and H2-m Is Prb-independentmentioning

confidence: 99%

pRB is required for interferon-γ-induction of the MHC class II Aβ gene

Zhu¹,

Pattenden

Bremner

1999

Oncogene

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“…For MHC class II molecules, newly synthesized ␣ and ␤ subunits are translocated into the endoplasmic reticulum, where they associate with the invariant chain (2). After transport to the trans-Golgi network, these ␣␤:invariant chain complexes are mainly sorted to endocytic pathways directly or transported to the cell surface and then internalized to the endocytic compartments, ultimately localizing to a specialized lysosomal compartment called the MHC class II compartment (MIIC) (3). In DCs exposed to Ag and maturational stimuli, such as LPS and TNF-␣, peptide loading is thought to occur in the MIIC, followed by transport of Ag-bound MHC class II molecules to the cell surface (4 -7).…”

Section: Endritic Cells (Dcs) 3 Capture Ags In Peripheral Tissuesmentioning

confidence: 99%

CD1 Molecules Efficiently Present Antigen in Immature Dendritic Cells and Traffic Independently of MHC Class II During Dendritic Cell Maturation

Cao

Sugita

Wel

et al. 2002

The Journal of Immunology

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Upon exposure to Ag and inflammatory stimuli, dendritic cells (DCs) undergo a series of dynamic cellular events, referred to as DC maturation, that involve facilitated peptide Ag loading onto MHC class II molecules and their subsequent transport to the cell surface. Besides MHC molecules, human DCs prominently express molecules of the CD1 family (CD1a, -b, -c, and -d) and mediate CD1-dependent presentation of lipid and glycolipid Ags to T cells, but the impact of DC maturation upon CD1 trafficking and Ag presentation is unknown. Using monocyte-derived immature DCs and those stimulated with TNF-α for maturation, we observed that none of the CD1 isoforms underwent changes in intracellular trafficking that mimicked MHC class II molecules during DC maturation. In contrast to the striking increase in surface expression of MHC class II on mature DCs, the surface expression of CD1 molecules was either increased only slightly (for CD1b and CD1c) or decreased (for CD1a). In addition, unlike MHC class II, DC maturation-associated transport from lysosomes to the plasma membrane was not readily detected for CD1b despite the fact that both molecules were prominently expressed in the same MIIC lysosomal compartments before maturation. Consistent with this, DCs efficiently presented CD1b-restricted lipid Ags to specific T cells similarly in immature and mature DCs. Thus, DC maturation-independent pathways for lipid Ag presentation by CD1 may play a crucial role in host defense, even before DCs are able to induce maximum activation of peptide Ag-specific T cells.

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“…In professional antigen-presenting cells, the organelles at which MHCII peptide loading occurs mainly constitute late endosomes, although lysosomes have also been implicated (Geuze 1998). Together, these endocytic compartments are also referred to as MHCII compartments (MIICs) (Peters et al 1991;Kleijmeer et al 1997Kleijmeer et al , 2001). DCs constitutively synthesize MHCII, which, in the absence of pathogen, are all loaded with "self " peptides in MIICs.…”

mentioning

confidence: 99%

MHC Class II Antigen Presentation by Dendritic Cells Regulated through Endosomal Sorting

Broeke

Wubbolts

Stoorvogel

2013

Cold Spring Harbor Perspectives in Biology

136

102

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For the initiation of adaptive immune responses, dendritic cells present antigenic peptides in association with major histocompatibility complex class II (MHCII) to naïve CD4 þ T lymphocytes. In this review, we discuss how antigen presentation is regulated through intracellular processing and trafficking of MHCII. Newly synthesized MHCII is chaperoned by the invariant chain to endosomes, where peptides from endocytosed pathogens can bind. In nonactivated dendritic cells, peptide-loaded MHCII is ubiquitinated and consequently sorted by the ESCRT machinery to intraluminal vesicles of multivesicular bodies, ultimately leading to lysosomal degradation. Ubiquitination of newly synthesized MHCII is blocked when dendritic cells are activated, now allowing its transfer to the cell surface. This mode of regulation for MHCII is a prime example of how molecular processing and sorting at multivesicular bodies can determine the expression of signaling receptors at the plasma membrane.

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Segregation of MHC class II molecules from MHC class I molecules in the Golgi complex for transport to lysosomal compartments

Cited by 620 publications

References 43 publications

pRB is required for interferon-γ-induction of the MHC class II Aβ gene

pRB is required for interferon-γ-induction of the MHC class II Aβ gene

CD1 Molecules Efficiently Present Antigen in Immature Dendritic Cells and Traffic Independently of MHC Class II During Dendritic Cell Maturation

MHC Class II Antigen Presentation by Dendritic Cells Regulated through Endosomal Sorting

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