B cells rapidly target antigen and surface-derived MHCII into peripheral degradative compartments.

Autor: Hernández-Pérez S; Institute of Biomedicine, and MediCity Research Laboratories, University of Turku, 20014 Turku, Finland.; Turku Bioscience, University of Turku and Åbo Akademi University, 20520 Turku, Finland., Vainio M; Institute of Biomedicine, and MediCity Research Laboratories, University of Turku, 20014 Turku, Finland.; Turku Bioscience, University of Turku and Åbo Akademi University, 20520 Turku, Finland., Kuokkanen E; Institute of Biomedicine, and MediCity Research Laboratories, University of Turku, 20014 Turku, Finland., Šuštar V; Institute of Biomedicine, and MediCity Research Laboratories, University of Turku, 20014 Turku, Finland., Petrov P; Institute of Biomedicine, and MediCity Research Laboratories, University of Turku, 20014 Turku, Finland.; Turku Bioscience, University of Turku and Åbo Akademi University, 20520 Turku, Finland., Forstén S; Institute of Biomedicine, and MediCity Research Laboratories, University of Turku, 20014 Turku, Finland.; Turku Bioscience, University of Turku and Åbo Akademi University, 20520 Turku, Finland., Paavola V; Institute of Biomedicine, and MediCity Research Laboratories, University of Turku, 20014 Turku, Finland., Rajala J; Institute of Biomedicine, and MediCity Research Laboratories, University of Turku, 20014 Turku, Finland., Awoniyi LO; Institute of Biomedicine, and MediCity Research Laboratories, University of Turku, 20014 Turku, Finland.; Turku Bioscience, University of Turku and Åbo Akademi University, 20520 Turku, Finland., Sarapulov AV; Institute of Biomedicine, and MediCity Research Laboratories, University of Turku, 20014 Turku, Finland.; Turku Bioscience, University of Turku and Åbo Akademi University, 20520 Turku, Finland., Vihinen H; Institute of Biotechnology, Electron Microscopy Unit, 00014 University of Helsinki, Finland., Jokitalo E; Institute of Biotechnology, Electron Microscopy Unit, 00014 University of Helsinki, Finland., Bruckbauer A; Facility for Imaging by Light Microscopy (FILM), National Heart and Lung Institute, Imperial College London, London SW7 2AZ, UK., Mattila PK; Institute of Biomedicine, and MediCity Research Laboratories, University of Turku, 20014 Turku, Finland pieta.mattila@utu.fi.; Turku Bioscience, University of Turku and Åbo Akademi University, 20520 Turku, Finland.
Jazyk: angličtina
Zdroj: Journal of cell science [J Cell Sci] 2019 Dec 20; Vol. 133 (5). Date of Electronic Publication: 2019 Dec 20.
DOI: 10.1242/jcs.235192
Abstrakt: In order to mount high-affinity antibody responses, B cells internalise specific antigens and process them into peptides loaded onto MHCII for presentation to T helper cells (T H cells). While the biochemical principles of antigen processing and MHCII loading have been well dissected, how the endosomal vesicle system is wired to enable these specific functions remains much less studied. Here, we performed a systematic microscopy-based analysis of antigen trafficking in B cells to reveal its route to the MHCII peptide-loading compartment (MIIC). Surprisingly, we detected fast targeting of internalised antigen into peripheral acidic compartments that possessed the hallmarks of the MIIC and also showed degradative capacity. In these vesicles, internalised antigen converged rapidly with membrane-derived MHCII and partially overlapped with cathepsin-S and H2-M, both required for peptide loading. These early compartments appeared heterogenous and atypical as they contained a mixture of both early and late endosomal markers, indicating a specialized endosomal route. Together, our data suggest that, in addition to in the previously reported perinuclear late endosomal MIICs, antigen processing and peptide loading could have already started in these specialized early peripheral acidic vesicles (eMIIC) to support fast peptide-MHCII presentation.
Competing Interests: Competing interestsThe authors declare no competing or financial interests.
(© 2019. Published by The Company of Biologists Ltd.)
Databáze: MEDLINE