Endosomal sorting of MHC class II determines antigen presentation by dendritic cells.
Dendritic cells (DCs) initiate primary immune responses by presenting pathogen-derived antigens in association with major histocompatibility Class II molecules (MHC II) to T cells. In DCs, MHC II is constitutively synthesized and loaded at endosomes with peptides from hydrolyzed endogenous proteins or exogenously acquired antigens. Whether peptide loaded MHC II (MHC II-p) is subsequently recruited to and stably expressed at the plasma membrane or degraded in lysosomes is determined by the status of the DC. In immature DCs, MHC II-p is ubiquitinated after peptide loading, driving its sorting to the luminal vesicles of multivesicular bodies. These luminal vesicles, and the MHC II-p they carry, are delivered to lysosomes for degradation. MHC II-p is inefficiently ubiquitinated in DCs that are activated by pathogens or inflammatory stimuli, thus allowing its transfer to and stable expression at the plasma membrane.
van Niel
Guillaume
G
Institut Curie, Centre National de la Recherche Scientifique-Unité Mixte de Recherche 144, Paris 75248, France. Guillaume.van-Niel@Curie.fr
Wubbolts
Richard
R
Stoorvogel
Willem
W
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000276:immunology; D054875:Ubiquitination
D000949:Histocompatibility Antigens Class II