Identification of a lysosomal peptide transport system induced during dendritic cell development
- The delivery of protein fragments to major histocompatibility complex (MHC)-loading compartments of professional antigen-presenting cells is essential in the adaptive immune response against pathogens. Apart from the crucial role of the transporter associated with antigen processing (TAP) for peptide loading of MHC class I molecules in the endoplasmic reticulum, TAP-independent translocation pathways have been proposed but not identified so far. Based on its overlapping substrate specificity with TAP, we herein investigated the ABC transporter ABCB9, also named TAP-like (TAPL). Remarkably, TAPL expression is strongly induced during differentiation of monocytes to dendritic cells and to macrophages. TAPL does not, however, restore MHC class I surface expression in TAP-deficient cells, demonstrating that TAPL alone or in combination with single TAP subunits does not form a functional transport complex required for peptide loading of MHC I in the endoplasmic reticulum. In fact, by using quantitative immunofluorescence and subcellular fractionation, TAPL was detected in the lysosomal compartment co-localizing with the lysosome-associated membrane protein LAMP-2. By in vitro assays, we demonstrate a TAPL-specific translocation of peptides into isolated lysosomes, which strictly requires ATP hydrolysis. These results suggest a mechanism by which antigenic peptides have access to the lysosomal compartment in professional antigen-presenting cells.
Verfasserangaben: | Özlem DemirelGND, Zoe WaiblerORCiDGND, Ulrich KalinkeORCiDGND, Frank GrünebachGND, Silke Appel, Peter BrossartGND, Andrej Hasilik, Robert TampéORCiDGND, Rupert AbeleORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-762781 |
DOI: | https://doi.org/10.1074/jbc.M708139200 |
ISSN: | 0021-9258 |
Pubmed-Id: | https://pubmed.ncbi.nlm.nih.gov/17977821 |
Titel des übergeordneten Werkes (Englisch): | Journal of biological chemistry |
Verlag: | American Society for Biochemistry and Molecular Biology Publications |
Verlagsort: | Bethesda, Md |
Dokumentart: | Wissenschaftlicher Artikel |
Sprache: | Englisch |
Datum der Veröffentlichung (online): | 04.01.2021 |
Jahr der Erstveröffentlichung: | 2007 |
Veröffentlichende Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Datum der Freischaltung: | 14.03.2024 |
Jahrgang: | 282.2007 |
Ausgabe / Heft: | 52 |
Seitenzahl: | 8 |
Erste Seite: | 37836 |
Letzte Seite: | 37843 |
Institute: | Biochemie, Chemie und Pharmazie / Biochemie und Chemie |
DDC-Klassifikation: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
Sammlungen: | Universitätspublikationen |
Lizenz (Deutsch): | Creative Commons - Namensnennung 4.0 |
Lizenz (Deutsch): | Creative Commons - CC BY - Namensnennung 4.0 International |