Your browser version may not work well with NCBI's Web applications. More information here...
1: Proc Natl Acad Sci U S A. 2008 Mar 4;105(9):3491-6. Epub 2008 Feb 27.
Related Articles, Links
Click here to read Click here to read Click here to read
MHC class II stabilization at the surface of human dendritic cells is the result of maturation-dependent MARCH I down-regulation.

De Gassart A, Camosseto V, Thibodeau J, Ceppi M, Catalan N, Pierre P, Gatti E.

Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, Case 906, 13288 Marseille Cedex 9, France.

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.

Publication Types:
PMID: 18305173 [PubMed - indexed for MEDLINE]

PMCID: PMC2265198