MHC class I ligands are recruited from the cytosolic peptide pool, whose size is likely to depend on the balance between peptide generation by the proteasome and peptide degradation by downstream peptidases. We asked what fraction of this pool is available for presentation, and how the size of this fraction is modulated by peptide affinity for the TAP transporters. A model epitope restricted by HLA-A2 and a series of epitope precursors with N-terminal extensions by single residues modifying TAP affinity were expressed in a system that allowed us to monitor and modulate cytosolic peptide copy numbers. We show that presentation varies strongly according to TAP affinities of the epitope precursors. The fraction of cytosolic peptides recruited for MHC presentation does not exceed 1% and is more than two logs lower for peptides with very low TAP affinities. Therefore, TAP affinity has a substantial impact on MHC class I Ag presentation.

Fruci, D., Lauvau, G., Saveanu, L., Amicosante, M., Butler, R., Polack, A., et al. (2003). Quantifying recruitment of cytosolic peptides for HLA class I presentation: impact of TAP transport, 170(6), 2977-2984.

Quantifying recruitment of cytosolic peptides for HLA class I presentation: impact of TAP transport

AMICOSANTE, MASSIMO;
2003-03-15

Abstract

MHC class I ligands are recruited from the cytosolic peptide pool, whose size is likely to depend on the balance between peptide generation by the proteasome and peptide degradation by downstream peptidases. We asked what fraction of this pool is available for presentation, and how the size of this fraction is modulated by peptide affinity for the TAP transporters. A model epitope restricted by HLA-A2 and a series of epitope precursors with N-terminal extensions by single residues modifying TAP affinity were expressed in a system that allowed us to monitor and modulate cytosolic peptide copy numbers. We show that presentation varies strongly according to TAP affinities of the epitope precursors. The fraction of cytosolic peptides recruited for MHC presentation does not exceed 1% and is more than two logs lower for peptides with very low TAP affinities. Therefore, TAP affinity has a substantial impact on MHC class I Ag presentation.
15-mar-2003
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/04 - PATOLOGIA GENERALE
English
Con Impact Factor ISI
Antigen Presentation; Animals; Green Fluorescent Proteins; Humans; Histocompatibility Antigen H-2D; Mice; Mice, Transgenic; Mice, Knockout; HLA-A2 Antigen; Epitopes, T-Lymphocyte; H-2 Antigens; Luminescent Proteins; Tumor Cells, Cultured; Transfection; T-Lymphocytes, Cytotoxic; Binding, Competitive; Cytosol; ATP-Binding Cassette Transporters; Cytotoxicity Tests, Immunologic; Peptides; Cell Line, Transformed; Protein Transport
Fruci, D., Lauvau, G., Saveanu, L., Amicosante, M., Butler, R., Polack, A., et al. (2003). Quantifying recruitment of cytosolic peptides for HLA class I presentation: impact of TAP transport, 170(6), 2977-2984.
Fruci, D; Lauvau, G; Saveanu, L; Amicosante, M; Butler, R; Polack, A; Ginhoux, F; Lemonnier, F; Firat, H; van Endert, P
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/107088
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