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dc.contributor.authorLuft, Ten
dc.contributor.authorRizkalla, Men
dc.contributor.authorTai, T Yen
dc.contributor.authorChen, Qen
dc.contributor.authorMacFarlan, R Ien
dc.contributor.authorDavis, Ian Den
dc.contributor.authorMaraskovsky, Eugeneen
dc.contributor.authorCebon, Jonathan Sen
dc.identifier.citationJournal of Immunology (baltimore, Md. : 1950); 167(5): 2529-37en
dc.description.abstractThis study investigates the differential capacity of TAP-deficient T2 cells, TAP-competent EBV cells, and immature and mature dendritic cells to present peptides to preformed CTL lines. It demonstrates that presentation of exogenous peptides involves peptide uptake and loading onto newly synthesized MHC class I molecules. This mechanism was best demonstrated for low affinity peptides in the presence of irrelevant peptides competing for HLA binding sites. Under these circumstances, inhibition of protein synthesis with cycloheximide or vesicular trafficking with brefeldin A significantly reduced the presentation of low affinity peptides. This was not restored by adding exogenous beta(2)-microglobulin to stabilize the MHC complex on the cell surface. In contrast, presentation of high affinity peptides was not sensitive to cycloheximide or brefeldin A, which suggests that different mechanisms may operate for presentation of high and low affinity peptides by TAP-competent cells. High affinity peptides can apparently compete with peptides in preloaded MHC class I molecules at the cell surface, whereas low affinity peptides require empty MHC molecules within cells. Accordingly, very high concentrations of exogenous low affinity peptides in conjunction with active MHC class I metabolism were required to allow successful presentation against a background of competing intracellular high affinity peptides in TAP-competent cells. These findings have implications for the design of peptide and protein-based vaccines.en
dc.subject.otherATP-Binding Cassette Transporters.immunology.metabolismen
dc.subject.otherAmino Acid Sequenceen
dc.subject.otherAntigen Presentation.physiologyen
dc.subject.otherAntigens, Neoplasmen
dc.subject.otherBinding, Competitiveen
dc.subject.otherCell Differentiationen
dc.subject.otherCell Lineen
dc.subject.otherCell Membrane.immunology.metabolismen
dc.subject.otherDendritic Cells.cytology.immunology.metabolismen
dc.subject.otherHLA-A2 Antigen.metabolismen
dc.subject.otherHistocompatibility Antigens Class I.metabolismen
dc.subject.otherIntracellular Fluid.immunology.metabolismen
dc.subject.otherMART-1 Antigenen
dc.subject.otherNeoplasm Proteins.genetics.immunology.metabolismen
dc.subject.otherT-Lymphocytes, Cytotoxic.immunologyen
dc.titleExogenous peptides presented by transporter associated with antigen processing (TAP)-deficient and TAP-competent cells: intracellular loading and kinetics of presentation.en
dc.typeJournal Articleen
dc.identifier.journaltitleJournal of Immunology (Baltimore, Md. : 1950)en
dc.identifier.affiliationMelbourne Tumor Biology Branch, Ludwig Institute for Cancer Research, Austin and Repatriation Medical Centre, Heidelberg, Victoria, Australiaen
dc.type.austinJournal Articleen
item.openairetypeJournal Article-
item.fulltextNo Fulltext- Newton-John Cancer Research Institute-
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