Biodegradable nanoparticles containing TLR3 or TLR9 agonists together with antigen enhance MHC-restricted presentation of the antigen.
The effects of intraphagosomal toll-like receptor (TLR) activation on the MHC-restricted presentation of exogenous antigen were examined in dendritic cells (DCs). For phagosomal targeting, nanoparticles containing both a TLR agonist and a model antigen, ovalbumin (OVA), were prepared using biodegradable polymer poly(D,L-lactic acid-co-glycolic acid) and were then opsonized with mouse IgG. After incubating mouse DCs with the nanoparticles, the efficacy of OVA peptide presentation was evaluated using OVA-specific CD8 and CD4 T cells. Inclusion of either the TLR3 agonist poly(I:C) or the TLR9 agonist CpG oligodeoxynucleotides (ODN) significantly increased and prolonged both MHC class I- and class II-restricted OVA presentation. Accordingly, the DCs that phagocytosed the nanoparticles containing poly(I:C) or CpG ODN together with OVA efficiently induced the proliferation of OVA-specific CD8 and CD4 T cells. The potency levels of poly(I:C) and CpG ODN in increasing the MHC-restricted presentation of the exogenous antigen appeared to be similar. A combination of the 2 TLR agonists was synergistic in increasing the MHC class I-restricted, but not the class II-restricted, presentation of exogenous antigen. These results show that IgG-opsonized biodegradable nanoparticles containing both intraphagosomal TLR agonists and antigens can be efficient carrier materials in inducing antigen-specific T cell responses.
Chungbuk National University, Cheongju, Korea.
Young-Ran
YR
Lee
Young-Hee
YH
Lee
Sun-A
SA
Im
In-Ho
IH
Yang
Ghe Whan
GW
Ahn
Kyungjae
K
Kim
Chong-Kil
CK
Lee
D000818:Animals; D017951:Antigen Presentation; D000941:Antigens / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D019344:Lactic Acid; D051379:Mice; D053758:Nanoparticles; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D010047:Ovalbumin / Q000276:immunology; D011070:Poly I-C / Q000494:pharmacology*; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D051196:Toll-Like Receptor 3 / Q000819:agonists* / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000819:agonists* / Q000378:metabolism
D000941:Antigens; C408982:CPG-oligonucleotide; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; D051196:Toll-Like Receptor 3; D051217:Toll-Like Receptor 9; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D010047:Ovalbumin; D011070:Poly I-C