TY  - JOUR
A1  - Demirel, Özlem
A1  - Waibler, Zoe
A1  - Kalinke, Ulrich
A1  - Grünebach, Frank
A1  - Appel, Silke
A1  - Brossart, Peter
A1  - Hasilik, Andrej
A1  - Tampé, Robert
A1  - Abele, Rupert
T1  - Identification of a lysosomal peptide transport system induced during dendritic cell development
T2  - Journal of biological chemistry
N2  - 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.
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/76278
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-762781
SN  - 0021-9258
VL  - 282.2007
IS  - 52
SP  - 37836
EP  - 37843
PB  - American Society for Biochemistry and Molecular Biology Publications
CY  - Bethesda, Md
ER  -