Mannose receptor mediated uptake of antigens strongly enhances HLA-class II restricted antigen presentation by cultured dendritic cells.
Dendritic cells (DCs) use macropinocytosis and mannose receptor mediated endocytosis for the uptake of exogenous antigens. Here we show that the endocytosis of the mannose receptor and mannosylated antigen is distinct from that of a non-mannosylated antigen. Shortly after internalization, however, both mannosylated and non-mannosylated antigen are found in an MIIC like compartment. The mannose receptor itself does not reach this compartment, and probably releases its ligand in an earlier endosomal structure. Finally, we found that mannosylation of peptides strongly enhanced their potency to stimulate HLA class II-restricted peptide-specific T cell clones. Our results indicate that mannosylation of antigen leads to selective targeting and subsequent superior presentation by DCs which may be useful for vaccine design.
Tan
M C
MC
Department of Immunohematology, Leiden University Hospital, The Netherlands.
Mommaas
A M
AM
Drijfhout
J W
JW
Jordens
R
R
Onderwater
J J
JJ
Verwoerd
D
D
Mulder
A A
AA
van der Heiden
A N
AN
Ottenhoff
T H
TH
Cella
M
M
Tulp
A
A
Neefjes
J J
JJ
Koning
F
F
D017951:Antigen Presentation; D000941:Antigens / Q000378:metabolism*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004705:Endocytosis; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D037181:Lectins, C-Type; D008024:Ligands; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011506:Proteins / Q000276:immunology / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000276:immunology*; D013347:Subcellular Fractions / Q000276:immunology / Q000378:metabolism
D000941:Antigens; D000949:Histocompatibility Antigens Class II; D037181:Lectins, C-Type; D008024:Ligands; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011506:Proteins; D011956:Receptors, Cell Surface