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Title: Exogenous peptides presented by transporter associated with antigen processing (TAP)-deficient and TAP-competent cells: intracellular loading and kinetics of presentation.
Austin Authors: Luft, T;Rizkalla, M;Tai, T Y;Chen, Q;MacFarlan, R I;Davis, Ian D;Maraskovsky, Eugene;Cebon, Jonathan S 
Melbourne Tumor Biology Branch, Ludwig Institute for Cancer Research, Austin and Repatriation Medical Centre, Heidelberg, Victoria, Australia
Issue Date: 1-Sep-2001
Publication information: Journal of Immunology (baltimore, Md. : 1950); 167(5): 2529-37
Abstract: This 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.
Gov't Doc #: 11509592
Journal: Journal of Immunology (Baltimore, Md. : 1950)
Type: Journal Article
Subjects: ATP-Binding Cassette Transporters.immunology.metabolism
Amino Acid Sequence
Antigen Presentation.physiology
Antigens, Neoplasm
Binding, Competitive
Cell Differentiation
Cell Line
Cell Membrane.immunology.metabolism
Dendritic Cells.cytology.immunology.metabolism
HLA-A2 Antigen.metabolism
Histocompatibility Antigens Class I.metabolism
Intracellular Fluid.immunology.metabolism
MART-1 Antigen
Neoplasm Proteins.genetics.immunology.metabolism
T-Lymphocytes, Cytotoxic.immunology
Appears in Collections:Journal articles

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