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

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

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. 2008 Mar 4;105(9):3491-6. doi: 10.1073/pnas.0708874105. Epub 2008 Feb 27.

PubMed ID
18305173 [ View in PubMed
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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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
HLA class II histocompatibility antigen, DR alpha chainP01903Details
HLA class II histocompatibility antigen, DRB1-15 beta chainP01911Details
HLA class II histocompatibility antigen, DR beta 3 chainP79483Details
HLA class II histocompatibility antigen, DR beta 4 chainP13762Details
HLA class II histocompatibility antigen, DR beta 5 chainQ30154Details