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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2008-7-28
pubmed:abstractText
Recently, much attention has been paid to cell-penetrating peptides (CPPs) as an antigen-delivery tool for presentation through the major histocompatibility complex class I (MHC-I) pathway. However, escape of CPPs from the endosome is inefficient and therefore a bottleneck for antigen delivery. Previously, we showed the importance of topological control of octaarginine (R8) peptides on the liposome surface for regulating cellular uptake as well as intracellular trafficking, especially endosomal escape. In this study, we hypothesized that efficient MHC-I presentation could be achieved by controlled intracellular trafficking of antigen encapsulated in R8-modified liposomes (R8-Lip). The mechanism of uptake of both R8-Lip and cationic liposomes was shown to be by macropinocytosis in dendritic cells. However, confocal laser scanning microscopy (CLSM) revealed that R8-Lip are able to release significantly more antigen to the cytosol than are cationic liposomes. Processing of the antigens delivered by R8-Lip was shown to be proteasome-dependent, which is consistent with selective antigen presentation by R8-Lip via MHC-I. According to antigen-presentation analysis, R8-Lip can induce significantly higher MHC-I presentation at lower doses than either soluble ovalbumin (OVA) or OVA in pH-sensitive or cationic liposomes. Moreover, R8-Lip showed an efficient antitumor effect in vivo. Therefore, R8-Lip is a promising new carrier for MHC-I-specific antigen presentation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1525-0024
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1507-14
pubmed:meshHeading
pubmed-meshheading:18560420-Acetylcysteine, pubmed-meshheading:18560420-Amiloride, pubmed-meshheading:18560420-Animals, pubmed-meshheading:18560420-Antigen Presentation, pubmed-meshheading:18560420-Bone Marrow Cells, pubmed-meshheading:18560420-Cell Line, Tumor, pubmed-meshheading:18560420-Cells, Cultured, pubmed-meshheading:18560420-Dendritic Cells, pubmed-meshheading:18560420-Flow Cytometry, pubmed-meshheading:18560420-Histocompatibility Antigens Class I, pubmed-meshheading:18560420-Intracellular Space, pubmed-meshheading:18560420-Liposomes, pubmed-meshheading:18560420-Mice, pubmed-meshheading:18560420-Mice, Inbred C57BL, pubmed-meshheading:18560420-Microscopy, Confocal, pubmed-meshheading:18560420-Neoplasms, Experimental, pubmed-meshheading:18560420-Nocodazole, pubmed-meshheading:18560420-Oligopeptides, pubmed-meshheading:18560420-Tumor Burden
pubmed:year
2008
pubmed:articleTitle
Efficient MHC class I presentation by controlled intracellular trafficking of antigens in octaarginine-modified liposomes.
pubmed:affiliation
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't