MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis
Sonja I Buschow
Department of Biochemistry and Cell Biology, Faculty of Veterinary Medicine and Institute of Biomembranes, Utrecht University, Utrecht, The Netherlands
Current address: Department of Tumor Immunology, NCMLS, Radboud University Nijmegen, Medical Centre, Nijmegen The Netherlands.
Search for more papers by this authorBas W M van Balkom
Department of Biomolecular Mass Spectrometry, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands
Current address: Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands.
Search for more papers by this authorMarian Aalberts
Department of Biochemistry and Cell Biology, Faculty of Veterinary Medicine and Institute of Biomembranes, Utrecht University, Utrecht, The Netherlands
Search for more papers by this authorAlbert J R Heck
Department of Biomolecular Mass Spectrometry, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands
Search for more papers by this authorMarca Wauben
Department of Biochemistry and Cell Biology, Faculty of Veterinary Medicine and Institute of Biomembranes, Utrecht University, Utrecht, The Netherlands
Search for more papers by this authorCorresponding Author
Willem Stoorvogel
Department of Biochemistry and Cell Biology, Faculty of Veterinary Medicine and Institute of Biomembranes, Utrecht University, Utrecht, The Netherlands
Professor W Stoorvogel, Department of Biochemistry and Cell Biology, Utrecht University, Yalelaan 2, PO Box 80.176, NL-3508 TD Utrecht, The Netherlands. E-mail: [email protected]Search for more papers by this authorSonja I Buschow
Department of Biochemistry and Cell Biology, Faculty of Veterinary Medicine and Institute of Biomembranes, Utrecht University, Utrecht, The Netherlands
Current address: Department of Tumor Immunology, NCMLS, Radboud University Nijmegen, Medical Centre, Nijmegen The Netherlands.
Search for more papers by this authorBas W M van Balkom
Department of Biomolecular Mass Spectrometry, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands
Current address: Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands.
Search for more papers by this authorMarian Aalberts
Department of Biochemistry and Cell Biology, Faculty of Veterinary Medicine and Institute of Biomembranes, Utrecht University, Utrecht, The Netherlands
Search for more papers by this authorAlbert J R Heck
Department of Biomolecular Mass Spectrometry, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands
Search for more papers by this authorMarca Wauben
Department of Biochemistry and Cell Biology, Faculty of Veterinary Medicine and Institute of Biomembranes, Utrecht University, Utrecht, The Netherlands
Search for more papers by this authorCorresponding Author
Willem Stoorvogel
Department of Biochemistry and Cell Biology, Faculty of Veterinary Medicine and Institute of Biomembranes, Utrecht University, Utrecht, The Netherlands
Professor W Stoorvogel, Department of Biochemistry and Cell Biology, Utrecht University, Yalelaan 2, PO Box 80.176, NL-3508 TD Utrecht, The Netherlands. E-mail: [email protected]Search for more papers by this authorThese authors contributed equally to this work.
Abstract
Professional antigen-presenting cells secrete major histocompatibility complex class II (MHC II) carrying exosomes with unclear physiological function(s). Exosomes are first generated as the intraluminal vesicles (ILVs) of a specific type of multivesicular body, and are then secreted by fusion of this compartment with the plasma membrane. We have previously shown that in contrast to the sorting of MHC II at lysosomally targeted multivesicular bodies, sorting of MHC II into exosomes does not rely on MHC II ubiquitination. In search for proteins that drive the incorporation of MHC II into exosomes or functionally discriminate exosomal from plasma membrane MHC II, we first analyzed the total proteome of highly purified B cell-derived exosomes using sensitive and accurate mass spectrometry (MS), and identified 539 proteins, including known and not previously identified constituents. Using quantitative MS, we then identified a small subset of proteins that were specifically co-immunoprecipitated with MHC II from detergent-solubilized exosomes. These include HSC71, HSP90, 14-3-3ε, CD20 and pyruvate kinase type M2 (PKM2), and we speculate on the functionality of their interaction with exosomal MHC II.
Supporting Information
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