PMID- 35947215 OWN - NLM STAT- MEDLINE DCOM- 20220812 LR - 20220915 IS - 1420-9071 (Electronic) IS - 1420-682X (Print) IS - 1420-682X (Linking) VI - 79 IP - 9 DP - 2022 Aug 10 TI - Nanoscale organization of the MHC I peptide-loading complex in human dendritic cells. PG - 477 LID - 10.1007/s00018-022-04472-2 [doi] LID - 477 AB - Dendritic cells (DCs) translate local innate immune responses into long-lasting adaptive immunity by priming antigen-specific T cells. Accordingly, there is an ample interest in exploiting DCs for therapeutic purposes, e.g., in personalized immunotherapies. Despite recent advances in elucidating molecular pathways of antigen processing, in DCs the exact spatial organization of the underlying processes is largely unknown. Here, we unraveled the nanoscale organization of the transporter associated with antigen processing (TAP)-dependent peptide-loading machinery in human monocyte-derived DCs (moDC). We detected an unexpected accumulation of MHC I peptide-loading complexes (PLCs) and TAP-dependent peptide compartmentalization in protrusions of activated DCs. Using single-molecule localization microscopy we revealed that PLCs display homogeneously sized assemblies, independent of the DC activation status or cellular localization. Our data indicate that moDCs show augmentation of subcellular PLC density during DC maturation. We observed a twofold density increase in the cell body, while an even fourfold accumulation was detected in the tips of the protrusions at the mature DC stage in comparison to immature DCs. In these tip regions, PLC assemblies are found along highly compressed tubular ER networks. These findings provide novel insights into nanoscale organization of the antigen presentation machinery, and open new perspectives on the T cell stimulatory capacity of DCs. CI - (c) 2022. The Author(s). FAU - Koller, Nicole AU - Koller N AD - Institute of Biochemistry, Biocenter, Goethe University Frankfurt, Max-von-Laue-Str. 9, 60438, Frankfurt am Main, Germany. FAU - Hollthaler, Philipp AU - Hollthaler P AD - Institute of Biochemistry, Biocenter, Goethe University Frankfurt, Max-von-Laue-Str. 9, 60438, Frankfurt am Main, Germany. FAU - Barends, Martina AU - Barends M AD - Institute of Biochemistry, Biocenter, Goethe University Frankfurt, Max-von-Laue-Str. 9, 60438, Frankfurt am Main, Germany. FAU - Doring, Marius AU - Doring M 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 the Hannover Medical School, 30625, Feodor-Lynen-Str. 7, Hannover, Germany. FAU - Spahn, Christoph AU - Spahn C AD - Institute of Physical and Theoretical Chemistry, Goethe University Frankfurt, Max-von-Laue-Str. 9, 60438, Frankfurt am Main, Germany. FAU - Duran, Veronica AU - Duran V 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 the Hannover Medical School, 30625, Feodor-Lynen-Str. 7, Hannover, Germany. FAU - Costa, Bibiana AU - Costa B 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 the Hannover Medical School, 30625, Feodor-Lynen-Str. 7, Hannover, 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 the Hannover Medical School, 30625, Feodor-Lynen-Str. 7, Hannover, Germany. FAU - Heilemann, Mike AU - Heilemann M AD - Institute of Physical and Theoretical Chemistry, Goethe University Frankfurt, Max-von-Laue-Str. 9, 60438, Frankfurt am Main, Germany. FAU - Kalinke, Ulrich AU - Kalinke U 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 the Hannover Medical School, 30625, Feodor-Lynen-Str. 7, Hannover, Germany. ulrich.kalinke@twinore.de. AD - Cluster of Excellence - Resolving Infection Susceptibility (RESIST), Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany. ulrich.kalinke@twinore.de. FAU - Tampe, Robert AU - Tampe R AUID- ORCID: 0000-0002-0403-2160 AD - Institute of Biochemistry, Biocenter, Goethe University Frankfurt, Max-von-Laue-Str. 9, 60438, Frankfurt am Main, Germany. tampe@em.uni-frankfurt.de. LA - eng GR - FOR 2830/P04/Deutsche Forschungsgemeinschaft/ GR - CRC807/P20/Deutsche Forschungsgemeinschaft/ GR - CRC807/P16/Deutsche Forschungsgemeinschaft/ GR - TA157/12-1/Deutsche Forschungsgemeinschaft/ GR - SFB 1507/Deutsche Forschungsgemeinschaft/ GR - DynaMem P03/Hessisches Ministerium fur Wissenschaft und Kunst/ GR - 798121/ERC_/European Research Council/International PT - Journal Article DEP - 20220810 PL - Switzerland TA - Cell Mol Life Sci JT - Cellular and molecular life sciences : CMLS JID - 9705402 RN - 0 (Histocompatibility Antigens Class I) RN - 0 (Peptides) SB - IM MH - Antigen Presentation MH - *Dendritic Cells/metabolism MH - *Histocompatibility Antigens Class I/metabolism MH - Humans MH - Monocytes/metabolism MH - Peptides/metabolism PMC - PMC9365725 OTO - NOTNLM OT - ABC transporter OT - Antigen processing OT - Membrane organization OT - Membrane proteins OT - Nanoscopy OT - Super-resolution microscopy COIS- The authors declare no conflict of interest. EDAT- 2022/08/11 06:00 MHDA- 2022/08/13 06:00 PMCR- 2022/08/10 CRDT- 2022/08/10 11:26 PHST- 2022/02/22 00:00 [received] PHST- 2022/07/05 00:00 [accepted] PHST- 2022/06/04 00:00 [revised] PHST- 2022/08/10 11:26 [entrez] PHST- 2022/08/11 06:00 [pubmed] PHST- 2022/08/13 06:00 [medline] PHST- 2022/08/10 00:00 [pmc-release] AID - 10.1007/s00018-022-04472-2 [pii] AID - 4472 [pii] AID - 10.1007/s00018-022-04472-2 [doi] PST - epublish SO - Cell Mol Life Sci. 2022 Aug 10;79(9):477. doi: 10.1007/s00018-022-04472-2.