Platelet EVs contain an active proteasome involved in protein processing for antigen presentation via MHC-I molecules

Genevieve Marcoux, Audrée Laroche, Stephan Hasse, Marie Bellio, Maroua Mbarik, Marie Tamagne, Isabelle Allaeys, Anne Zufferey, Tania Lévesque, Johan Rebetz, Annie Karakeussian-Rimbaud, Julie Turgeon, Sylvain G Bourgoin, Hind Hamzeh-Cognasse, Fabrice Cognasse, Rick Kapur, John W Semple, Marie-Josée Hébert, France Pirenne, Herman S OverkleeftBogdan I Florea, Mélanie Dieude, Benoît Vingert, Eric Boilard

Research output: Contribution to journalArticlepeer-review


In addition to their hemostatic role, platelets play a significant role in immunity. Once activated, platelets release extracellular vesicles (EVs) formed by the budding of their cytoplasmic membranes. Because of their heterogeneity, platelet EVs (PEVs) are thought to perform diverse functions. It is unknown, however, whether the proteasome is transferred from platelets to PEVs or whether its function is retained. We hypothesized that functional protein processing and antigen presentation machinery are transferred to PEVs by activated platelets. Using molecular and functional assays, we found that the active 20S proteasome was enriched in PEVs, along with major histocompatibility complex class I (MHC-I) and lymphocyte costimulatory molecules (CD40L and OX40L). Proteasome-containing PEVs were identified in healthy donor blood, but did not increase in platelet concentrates that caused adverse transfusion reactions. They were augmented, however, after immune complex injections in mice. The complete biodistribution of murine PEVs after injection into mice revealed that they principally reached lymphoid organs, such as spleen and lymph nodes, in addition to the bone marrow, and to a lesser extent, liver and lungs. The PEV proteasome processed exogenous ovalbumin (OVA) and loaded its antigenic peptide onto MHC-I molecules, which promoted OVA-specific CD8+ T-lymphocyte proliferation. These results suggest that PEVs contribute to adaptive immunity through cross-presentation of antigens and have privileged access to immune cells through the lymphatic system, a tissue location that is inaccessible to platelets.

Original languageEnglish
Pages (from-to)2607-2620
Issue number25
Publication statusPublished - 2021 Dec 23

Bibliographical note

© 2021 by The American Society of Hematology.

Subject classification (UKÄ)

  • Hematology

Free keywords

  • Animals
  • Antigen Presentation
  • Blood Platelets/chemistry
  • Extracellular Vesicles/chemistry
  • Histocompatibility Antigens Class I/analysis
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Proteasome Endopeptidase Complex/analysis


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