Membrane insertion and oligomeric assembly of HLA-DR histocompatibility antigens

Kvist, Sune; Wiman, Klas G.; Claesson, Lena; Peterson, Per A.; Dobberstein, Bernhard

doi:10.1016/0092-8674(82)90090-3

Cited by 296 publications

(180 citation statements)

References 36 publications

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“…DR 3' chains present in the oligomeric complex with DR a and/3 moieties undergo intracellular transport and, subsequently, are detached from the oligomeric complex that finally appears on the cell surface (9,14). The ultimate fate of the DR 3' chain is unknown.…”

Section: Resultsmentioning

confidence: 99%

“…HLA-DR antigens represent the human analogue to murine I-E antigens (6), whereas HLA-DS (7) or DC 1 antigens (8) correspond to murine I-A molecules. HLA-DR oligomers are formed by the noncovalent association of three po]ypeptides, i.e., a, /3, and 3' chains (9). As opposed to a and/3 chains the 3' chain appears to be invariant, at least by charge and mass, regardless of the DR phenotype (10,11).…”

mentioning

confidence: 99%

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Evidence of HLA-DR antigen biosynthesis by human keratinocytes in disease.

Volc‐Platzer¹,

Majdic²,

Knapp³

et al. 1984

The Journal of Experimental Medicine

162

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As opposed to normal human skin where HLA-DR expression is restricted to the Langerhans cell (LC) population, HLA-DR, but not HLA-DS antigens can be readily detected on keratinocytes (KC) in certain disease states, i.e., cutaneous T cell lymphoma (CTCL), graft-vs-host disease (GVHD), and lichen planus (LP). To clarify the cellular origin of KC-bound HLA-DR antigens, we used a monoclonal antibody directed against determinants solely expressed on the cytoplasmic HLA-DR gamma chain (VIC-Y1) and observed that, by immunofluorescence, KC displaying HLA-DR alpha/beta complexes on their surface uniformly displayed cytoplasmic VIC-Y1 reactivity. In view of the crucial role of the gamma chain for HLA-DR biosynthesis, we conclude that HLA-DR antigens on KC are actively synthesized by these cells.

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Evidence of HLA-DR antigen biosynthesis by human keratinocytes in disease.

Volc‐Platzer¹,

Majdic²,

Knapp³

et al. 1984

The Journal of Experimental Medicine

162

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“…This shows that trimerization is not induced by the N-terminal cytosolic tail although NMR studies have shown that a peptide representing the tail is found as a homotrimer. 2 Various chemical cross-linkers were generally needed to stabilize the multimers, but trimers of p35* hIi, p33 hIi, and ⌬20 hIi were also detected under nonreducing conditions without the use of cross-linker. This might indicate that parts of the cytosolic tail of Ii have a stabilizing effect on the trimer after its induction.…”

Section: Discussionmentioning

confidence: 99%

“…Invariant chain (Ii) is a type II transmembrane protein that associates with the major histocompatibility complex (MHC) class II molecules in the endoplasmic reticulum (ER) (1,2). The formation of the ␣␤Ii complex occurs by the sequential addition of one ␣-and one ␤-chain to a pre-existing core of trimeric Ii molecules (3,4).…”

mentioning

confidence: 99%

Exon 6 Is Essential for Invariant Chain Trimerization and Induction of Large Endosomal Structures

Gedde-Dahl

Freisewinkel

Staschewski

et al. 1997

Journal of Biological Chemistry

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Invariant chain (Ii) is a transmembrane type II protein that forms a complex with the major histocompatibility complex (MHC) class II molecules in the endoplasmic reticulum (ER). The membrane proximal luminal region of Ii is responsible for the non-covalent association with MHC class II molecules. Chemical cross-linking in COS cells was used to study the effect of luminal and cytoplasmic deletions on trimerization of Ii. We demonstrate that trimerization of Ii is independent of the cytosolic tail of Ii, whereas residues 162-191 (the sequence encoded by exon 6) in the luminal part of Ii are essential for trimer formation. Immunofluorescence studies of the transfected luminal deletion constructs show that the amino acids encoded by exon 6 of Ii are also essential for the induction of large endosomal vesicles. The data suggest that Ii must be in a trimeric form to modify the endosomal pathway.

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“…Ii binds the MHCII peptide-binding groove with a region in its luminal domain that is called CLIP (for class-II-associated invariant chain peptide) (Rudensky et al 1991;Chicz et al 1992;Riberdy et al 1992;Sette et al 1992;Freisewinkel et al 1993). Normally, Ii is synthesized in excess over MHCII, ensuring Ii rather than peptide binding to MHCII (Kvist et al 1982;Sekaly et al 1986;Marks et al 1990;Pieters et al 1991). Peptides that are transferred into the ER by TAP, for potential binding to MHCI, indeed have poor potential to bind MHCII (Bikoff et al 1993;Viville et al 1993;Elliott et al 1994;Romagnoli and Germain 1994;Busch et al 1996).…”

Section: Biosynthesis Of Mhciimentioning

confidence: 99%

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

Broeke

Wubbolts

Stoorvogel

2013

Cold Spring Harbor Perspectives in Biology

139

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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Membrane insertion and oligomeric assembly of HLA-DR histocompatibility antigens

Cited by 296 publications

References 36 publications

Evidence of HLA-DR antigen biosynthesis by human keratinocytes in disease.

Evidence of HLA-DR antigen biosynthesis by human keratinocytes in disease.

Exon 6 Is Essential for Invariant Chain Trimerization and Induction of Large Endosomal Structures

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

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