PMID- 30867143 OWN - NLM STAT- MEDLINE DCOM- 20200327 LR - 20200327 IS - 2473-9537 (Electronic) IS - 2473-9529 (Print) IS - 2473-9529 (Linking) VI - 3 IP - 6 DP - 2019 Mar 26 TI - Modulation of TAP-dependent antigen compartmentalization during human monocyte-to-DC differentiation. PG - 839-850 LID - 10.1182/bloodadvances.2018027268 [doi] AB - Dendritic cells (DCs) take up antigen in the periphery, migrate to secondary lymphoid organs, and present processed antigen fragments to adaptive immune cells and thus prime antigen-specific immunity. During local inflammation, recirculating monocytes are recruited from blood to the inflamed tissue, where they differentiate to macrophages and DCs. In this study, we found that monocytes showed high transporter associated with antigen processing (TAP)-dependent peptide compartmentalization and that after antigen pulsing, they were not able to efficiently stimulate antigen-specific T lymphocytes. Nevertheless, upon in vitro differentiation to monocyte-derived DCs, TAP-dependent peptide compartmentalization as well as surface major histocompatibility complex I turnover decreased and the cells efficiently restimulated T lymphocytes. Although TAP-dependent peptide compartmentalization decreased during DC differentiation, TAP expression levels increased. Furthermore, TAP relocated from early endosomes in monocytes to the endoplasmic reticulum (ER) and lysosomal compartments in DCs. Collectively, these data are compatible with the model that during monocyte-to-DC differentiation, the subcellular relocation of TAP and the regulation of its activity assure spatiotemporal separation of local antigen uptake and processing by monocytes and efficient T-lymphocyte stimulation by DCs. CI - (c) 2019 by The American Society of Hematology. FAU - Doring, Marius AU - Doring M AUID- ORCID: 0000-0002-5278-8376 AD - Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research and Hannover Medical School, Hannover, Germany. FAU - Blees, Hanna AU - Blees H AD - Institute of Biochemistry, Biocenter, Goethe University Frankfurt, Frankfurt, Germany. FAU - Koller, Nicole AU - Koller N AD - Institute of Biochemistry, Biocenter, Goethe University Frankfurt, Frankfurt, Germany. FAU - Tischer-Zimmermann, Sabine AU - Tischer-Zimmermann S AUID- ORCID: 0000-0003-2326-0342 AD - Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany. FAU - Musken, Mathias AU - Musken M AUID- ORCID: 0000-0002-5624-1378 AD - Institute of Molecular Bacteriology, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research and Hannover Medical School, Hannover, Germany. AD - Department of Molecular Bacteriology, Helmholtz Centre for Infection Research, Braunschweig, Germany. FAU - Henrich, Frederik AU - Henrich F AD - Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research and Hannover Medical School, Hannover, Germany. AD - Institute of Biochemistry, Biocenter, Goethe University Frankfurt, Frankfurt, Germany. FAU - Becker, Jennifer AU - Becker J AD - Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research and Hannover Medical School, Hannover, Germany. FAU - Grabski, Elena AU - Grabski E AD - Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research and Hannover Medical School, Hannover, Germany. FAU - Wang, Junxi AU - Wang J AD - Biostatistics, Helmholtz Centre for Infection Research, Braunschweig, Germany. FAU - Janssen, Hans AU - Janssen H AD - Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. FAU - Zuschratter, Werner AU - Zuschratter W AD - Leibniz Institute for Neurobiology, Magdeburg, Germany. FAU - Neefjes, Jacques AU - Neefjes J AUID- ORCID: 0000-0001-6763-2211 AD - Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. FAU - Klawonn, Frank AU - Klawonn F AUID- ORCID: 0000-0001-9613-182X AD - Biostatistics, Helmholtz Centre for Infection Research, Braunschweig, Germany. AD - Department of Computer Science, Ostfalia University of Applied Sciences, Wolfenbuttel, Germany. FAU - Eiz-Vesper, Britta AU - Eiz-Vesper B AD - Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany. FAU - Tampe, Robert AU - Tampe R AUID- ORCID: 0000-0002-0403-2160 AD - Institute of Biochemistry, Biocenter, Goethe University Frankfurt, Frankfurt, Germany. AD - Cluster of Excellence Frankfurt-Macromolecular Complexes, Goethe University Frankfurt, Frankfurt, Germany; and. FAU - Kalinke, Ulrich AU - Kalinke U AUID- ORCID: 0000-0003-0503-9564 AD - Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research and Hannover Medical School, Hannover, Germany. AD - Cluster of Excellence-Resolving Infection Susceptibility, Hannover Medical School, Hannover, Germany. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Blood Adv JT - Blood advances JID - 101698425 RN - 0 (ATP-Binding Cassette Transporters) RN - 0 (transporter associated with antigen processing (TAP)) SB - IM MH - ATP-Binding Cassette Transporters/*metabolism MH - Antigen Presentation/immunology MH - *Cell Compartmentation MH - Cell Differentiation/*immunology MH - Cells, Cultured MH - Dendritic Cells/*cytology/immunology MH - Humans MH - Lysosomes/metabolism MH - Monocytes/*cytology/immunology MH - T-Lymphocytes/immunology PMC - PMC6436010 COIS- Conflict-of-interest disclosure: The authors declare no competing financial interests. EDAT- 2019/03/15 06:00 MHDA- 2020/03/28 06:00 PMCR- 2019/03/13 CRDT- 2019/03/15 06:00 PHST- 2018/10/12 00:00 [received] PHST- 2019/02/13 00:00 [accepted] PHST- 2019/03/15 06:00 [entrez] PHST- 2019/03/15 06:00 [pubmed] PHST- 2020/03/28 06:00 [medline] PHST- 2019/03/13 00:00 [pmc-release] AID - bloodadvances.2018027268 [pii] AID - 2018/027268 [pii] AID - 10.1182/bloodadvances.2018027268 [doi] PST - ppublish SO - Blood Adv. 2019 Mar 26;3(6):839-850. doi: 10.1182/bloodadvances.2018027268.