MHC class II stabilization at the surface of human dendritic cells is the result of maturation-dependent MARCH I down-regulation. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2008

MHC class II stabilization at the surface of human dendritic cells is the result of maturation-dependent MARCH I down-regulation.

Résumé

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.

Domaines

Immunologie

Dates et versions

hal-00294205 , version 1 (08-07-2008)

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Citer

Aude de Gassart, Voahirana Camosseto, Jacques Thibodeau, Maurizio Ceppi, Nadia Catalan, et al.. MHC class II stabilization at the surface of human dendritic cells is the result of maturation-dependent MARCH I down-regulation.. Proceedings of the National Academy of Sciences of the United States of America, 2008, 105 (9), pp.3491-6. ⟨10.1073/pnas.0708874105⟩. ⟨hal-00294205⟩

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