Mannose receptor-mediated uptake of antigens strongly enhances HLA class II-restricted antigen presentation by cultured dendritic cells

被引:263
作者
Tan, MCAA
Mommaas, AM
Drijfhout, JW
Jordens, R
Onderwater, JJM
Verwoerd, D
Mulder, AA
vanderHeiden, AN
Scheidegger, D
Oomen, LCJM
Ottenhoff, THM
Tulp, A
Neefjes, JJ
Koning, F
机构
[1] LEIDEN UNIV,MED CTR,DEPT IMMUNOHEMATOL & BLOOD BANK,NL-2300 RC LEIDEN,NETHERLANDS
[2] LEIDEN UNIV,MED CTR,ELECTRON MICROSCOPY LAB,LEIDEN,NETHERLANDS
[3] LEIDEN UNIV,MED CTR,DEPT DERMATOL,LEIDEN,NETHERLANDS
[4] NETHERLANDS CANC INST,DIV CELLULAR BIOCHEM,NL-1066 CX AMSTERDAM,NETHERLANDS
[5] NETHERLANDS CANC INST,DIV CELBIOL,AMSTERDAM,NETHERLANDS
[6] BASEL INST IMMUNOL,BASEL,SWITZERLAND
关键词
mannose receptor; major histocompatibility complex class II-restricted antigen presentation mannosylated antigens;
D O I
10.1002/eji.1830270942
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Dendritic cells (DC) efficiently take up antigens by macropinocytosis and mannose receptor-mediated endocytosis. Here we show that endocytosis of mannose receptor-antigen complexes takes glace via small coated vesicles, while non-mannosylated antigens were mainly present in larger vesicles, Shortly after internalization the mannose receptor and its ligand appeared in the larger vesicles. Within 10 min, the mannosylated and non-mannosylated antigens co-localized with typical markers for major histocompatibility complex class II-enriched compartments and lysosomes. In contrast, the mannose receptor appeared not to reach these compartments, suggesting that it releases its ligand in an earlier endosomal structure. Moreover wee demonstrate that mannosylation of protein antigen and peptides resulted in a 280-10000-fold enhanced potency to stimulate HLA class II-restricted peptide-specific T cell clones compared to non-mannosylated peptides. Our results indicate that mannosylation of antigen leads to selective targeting and subsequent superior presentation by DC which may be applicable in vaccine design.
引用
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页码:2426 / 2435
页数:10
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