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http://purl.uniprot.org/citations/17462991http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/17462991http://www.w3.org/2000/01/rdf-schema#comment"Covalent conjugation of Toll-like receptor ligands (TLR-L) to synthetic antigenic peptides strongly improves antigen presentation in vitro and T lymphocyte priming in vivo. These molecularly well defined TLR-L-peptide conjugates, constitute an attractive vaccination modality, sharing the peptide antigen and a defined adjuvant in one single molecule. We have analyzed the intracellular trafficking and processing of two TLR-L conjugates in dendritic cells (DCs). Long synthetic peptides containing an ovalbumin cytotoxic T-cell epitope were chemically conjugated to two different TLR-Ls the TLR2 ligand, Pam(3)CysSK(4) (Pam) or the TLR9 ligand CpG. Rapid and enhanced uptake of both types of TLR-L-conjugated peptide occurred in DCs. Moreover, TLR-L conjugation greatly enhanced antigen presentation, a process that was dependent on endosomal acidification, proteasomal cleavage, and TAP translocation. The uptake of the CpG approximately conjugate was independent of endosomally-expressed TLR9 as reported previously. Unexpectedly, we found that Pam approximately conjugated peptides were likewise internalized independently of the expression of cell surface-expressed TLR2. Further characterization of the uptake mechanisms revealed that TLR2-L employed a different uptake route than TLR9-L. Inhibition of clathrin- or caveolin-dependent endocytosis greatly reduced uptake and antigen presentation of the Pam-conjugate. In contrast, internalization and antigen presentation of CpG approximately conjugates was independent of clathrin-coated pits but partly dependent on caveolae formation. Importantly, in contrast to the TLR-independent uptake of the conjugates, TLR expression and downstream TLR signaling was required for dendritic cell maturation and for priming of naïve CD8(+) T-cells. Together, our data show that targeting to two distinct TLRs requires distinct uptake mechanism but follows similar trafficking and intracellular processing pathways leading to optimal antigen presentation and T-cell priming."xsd:string
http://purl.uniprot.org/citations/17462991http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m701705200"xsd:string
http://purl.uniprot.org/citations/17462991http://purl.uniprot.org/core/author"Khan S."xsd:string
http://purl.uniprot.org/citations/17462991http://purl.uniprot.org/core/author"van der Marel G.A."xsd:string
http://purl.uniprot.org/citations/17462991http://purl.uniprot.org/core/author"Filippov D.V."xsd:string
http://purl.uniprot.org/citations/17462991http://purl.uniprot.org/core/author"Overkleeft H.S."xsd:string
http://purl.uniprot.org/citations/17462991http://purl.uniprot.org/core/author"Adema G.J."xsd:string
http://purl.uniprot.org/citations/17462991http://purl.uniprot.org/core/author"Ossendorp F."xsd:string
http://purl.uniprot.org/citations/17462991http://purl.uniprot.org/core/author"Melief C.J."xsd:string
http://purl.uniprot.org/citations/17462991http://purl.uniprot.org/core/author"Drijfhout J.W."xsd:string
http://purl.uniprot.org/citations/17462991http://purl.uniprot.org/core/author"Tanke H.J."xsd:string
http://purl.uniprot.org/citations/17462991http://purl.uniprot.org/core/author"van Hall T."xsd:string
http://purl.uniprot.org/citations/17462991http://purl.uniprot.org/core/author"Bijker M.S."xsd:string
http://purl.uniprot.org/citations/17462991http://purl.uniprot.org/core/author"van der Burg S.H."xsd:string
http://purl.uniprot.org/citations/17462991http://purl.uniprot.org/core/author"Weterings J.J."xsd:string
http://purl.uniprot.org/citations/17462991http://purl.uniprot.org/core/date"2007"xsd:gYear
http://purl.uniprot.org/citations/17462991http://purl.uniprot.org/core/name"J Biol Chem"xsd:string
http://purl.uniprot.org/citations/17462991http://purl.uniprot.org/core/pages"21145-21159"xsd:string
http://purl.uniprot.org/citations/17462991http://purl.uniprot.org/core/title"Distinct uptake mechanisms but similar intracellular processing of two different toll-like receptor ligand-peptide conjugates in dendritic cells."xsd:string
http://purl.uniprot.org/citations/17462991http://purl.uniprot.org/core/volume"282"xsd:string
http://purl.uniprot.org/citations/17462991http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/17462991
http://purl.uniprot.org/citations/17462991http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/17462991
http://purl.uniprot.org/uniprot/#_A0A068BER1-mappedCitation-17462991http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/17462991
http://purl.uniprot.org/uniprot/#_F6QHF1-mappedCitation-17462991http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/17462991
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