Differential MHC class II synthesis and ubiquitination confers distinct antigen-presenting properties on conventional and plasmacytoid dendritic cells.
The importance of conventional dendritic cells (cDCs) in the processing and presentation of antigen is well established, but the contribution of plasmacytoid dendritic cells (pDCs) to these processes, and hence to T cell immunity, remains unclear. Here we showed that unlike cDCs, pDCs continued to synthesize major histocompatibility complex (MHC) class II molecules and the MHC class II ubiquitin ligase MARCH1 long after activation. Sustained MHC class II-peptide complex formation, ubiquitination and turnover rendered pDCs inefficient in the presentation of exogenous antigens but enabled pDCs to continuously present endogenous viral antigens in their activated state. As the antigen-presenting abilities of cDCs and pDCs are fundamentally distinct, these two cell types may activate largely nonoverlapping repertoires of CD4(+) T cells.
The Walter and Eliza Hall Institute of Medical Research, University of Melbourne, Parkville, Victoria 3050, Australia.
Louise J
LJ
Young
Nicholas S
NS
Wilson
Petra
P
Schnorrer
Anna
A
Proietto
Toine
T
ten Broeke
Yohei
Y
Matsuki
Adele M
AM
Mount
Gabrielle T
GT
Belz
Meredith
M
O'Keeffe
Mari
M
Ohmura-Hoshino
Satoshi
S
Ishido
Willem
W
Stoorvogel
William R
WR
Heath
Ken
K
Shortman
Jose A
JA
Villadangos
D000818:Animals; D017951:Antigen Presentation; D000956:Antigens, Viral / Q000276:immunology; D018845:CD11 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000378:metabolism*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis / Q000235:genetics; D054875:Ubiquitination
D000956:Antigens, Viral; D018845:CD11 Antigens; D000949:Histocompatibility Antigens Class II; C545340:MARCH1 protein, mouse; D044767:Ubiquitin-Protein Ligases; D017493:Leukocyte Common Antigens