Dendritic cells process antigens encapsulated in a biodegradable polymer, poly(D,L-lactide-co-glycolide), via an alternate class I MHC processing pathway.
Biodegradable nanospheres generated from a biocompatible polymer, poly(D,L-lactide-co-glycolide) (PLGA), have been studied extensively as implantable reservoirs for sustained-release drug delivery. PLGA-nanospheres have also been studied as vehicles to deliver antigens to phagocytes. The intracellular processing pathway of antigens delivered to phagocytes by PLGA particles was studied in the present study. Ovalbumin (OVA) encapsulated with PLGA (OVA-nanosphere) was efficiently captured, processed and presented on class I major histocompatibility complex (MHC-I) by dendritic cells (DCs). The MHC-I processing of OVA-nanospheres was resistant to lactacystin, a proteosome inhibitor, and brefeldin A, which blocks anterograde transport from the endoplasmic reticulum (ER) through the Golgi apparatus. Chloroquine, which inhibits phagolysosomal enzymes by increasing phagolysosomal pH, inhibited MHC-I processing of OVA-nanospheres. In addition, DCs generated from TAP-/- mice were markedly suppressed in MHC-I processing of OVA-nanospheres. These results demonstrate that DCs process phagocytosed OVA-nanospheres via a vacuolar alternate MHC-I pathway for presentation of OVA peptides to T lymphocytes.
Gerelchuluun
Turmunkh
T
College of Pharmacy, Chungbuk National University, Cheongju 361-763, Korea.
Lee
Young-Hee
YH
Lee
Young-Ran
YR
Im
Sun-A
SA
Song
Sukgil
S
Park
Jeong Sook
JS
Han
Kun
K
Kim
Kyungjae
K
Lee
Chong-Kil
CK
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000502:physiology; D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D017951:Antigen Presentation; D020126:Brefeldin A / Q000494:pharmacology; D002460:Cell Line; D002738:Chloroquine / Q000494:pharmacology; D003713:Dendritic Cells / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D006801:Humans; D019344:Lactic Acid / Q000008:administration & dosage*; D054118:Nanospheres; D010047:Ovalbumin / Q000276:immunology*; D010587:Phagocytosis; D011100:Polyglycolic Acid / Q000008:administration & dosage*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage*
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D015395:Histocompatibility Antigens Class I; D011108:Polymers; C073119:TAP1 protein, human; C067713:lactacystin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D020126:Brefeldin A; D011100:Polyglycolic Acid; D019344:Lactic Acid; D002738:Chloroquine; D010047:Ovalbumin; D000111:Acetylcysteine