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

Doriana Fruci, Grégoire Lauvau, Loredana Saveanu, Massimo Amicosante, Richard H. Butler, Axel Polack, Florent Ginhoux, François Lemonnier, Hüseyin Firat, Peter M. Van Endert

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)2977-2984
Number of pages8
JournalJournal of Immunology
Volume170
Issue number6
Publication statusPublished - Mar 15 2003

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ASJC Scopus subject areas

  • Immunology

Cite this

Fruci, D., Lauvau, G., Saveanu, L., Amicosante, M., Butler, R. H., Polack, A., Ginhoux, F., Lemonnier, F., Firat, H., & Van Endert, P. M. (2003). Quantifying recruitment of cytosolic peptides for HLA class I presentation: Impact of TAP transport. Journal of Immunology, 170(6), 2977-2984.