MHC class II expression is regulated in dendritic cells independently of invariant chain degradation.
We have investigated the mechanisms that control MHC class II (MHC II) expression in immature and activated dendritic cells (DC) grown from spleen and bone marrow precursors. Degradation of the MHC II chaperone invariant chain (Ii), acquisition of peptide cargo by MHC II, and delivery of MHC II-peptide complexes to the cell surface proceeded similarly in both immature and activated DC. However, immature DC reendocytosed and then degraded the MHC II-peptide complexes much faster than the activated DC. MHC II expression in DC is therefore not controlled by the activity of the protease(s) that degrade Ii, but by the rate of endocytosis of peptide-loaded MHC II. Late after activation, DC downregulated MHC II synthesis both in vitro and in vivo.
Villadangos
J A
JA
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia. villadangos@wehi.edu.au
Cardoso
M
M
Steptoe
R J
RJ
van Berkel
D
D
Pooley
J
J
Carbone
F R
FR
Shortman
K
K
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis / Q000276:immunology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D002403:Cathepsins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D004705:Endocytosis / Q000276:immunology; D005786:Gene Expression Regulation; D005802:Genes, MHC Class II; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D010455:Peptides / Q000276:immunology
D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; D010455:Peptides; C045084:invariant chain; D002403:Cathepsins; C028217:cathepsin S