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PMID:18305173

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Citation

De Gassart, A, Camosseto, V, Thibodeau, J, Ceppi, M, Catalan, N, Pierre, P and Gatti, E (2008) MHC class II stabilization at the surface of human dendritic cells is the result of maturation-dependent MARCH I down-regulation. Proc. Natl. Acad. Sci. U.S.A. 105:3491-6

Abstract

In response to Toll-like receptor ligands, dendritic cells (DCs) dramatically enhance their antigen presentation capacity by stabilizing at the cell-surface MHC II molecules. We demonstrate here that, in human monocyte-derived DCs, the RING-CH ubiquitin E3 ligase, membrane-associated RING-CH I (MARCH I), promotes the ubiquitination of the HLA-DR beta-chain. Thus, in nonactivated DCs, MARCH I induces the surface internalization of mature HLA-DR complexes, therefore reducing their stability and levels. We further demonstrate that the maturation-dependent down-regulation of MARCH I is a key event in MHC class II up-regulation at the surface of LPS-activated DCs. MARCH I is, therefore, a major regulator of HLA-DR traffic, and its loss contributes to the acquisition of the potent immunostimulatory properties of mature human DCs.

Links

PubMed PMC2265198 Online version:10.1073/pnas.0708874105

Keywords

Antigens, Surface; Biological Transport; Cells, Cultured; Dendritic Cells/immunology; Down-Regulation/genetics; Endocytosis; HLA-DR Antigens/metabolism; Histocompatibility Antigens Class II/metabolism; Humans; Lipopolysaccharides/pharmacology; Ubiquitin-Protein Ligases/genetics

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:DRA

located_in

GO:0005765: lysosomal membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:DRA

located_in

GO:0031902: late endosome membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:DRB1

located_in

GO:0005765: lysosomal membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:DRB1

located_in

GO:0031902: late endosome membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:DRB4

located_in

GO:0005765: lysosomal membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:DRB4

located_in

GO:0031902: late endosome membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:DRB3

located_in

GO:0005765: lysosomal membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:DRB3

located_in

GO:0031902: late endosome membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:DRB5

located_in

GO:0005765: lysosomal membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:DRB5

located_in

GO:0031902: late endosome membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:MARH1

enables

GO:0061630: ubiquitin protein ligase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:2B1E

part_of

GO:0005765: lysosomal membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:2B1E

part_of

GO:0031902: late endosome membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:MARH1

enables

GO:0004842: ubiquitin-protein transferase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:MARH1

involved_in

GO:0006955: immune response

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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