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

Marcoux, Genevieve LU ; Laroche, Audrée ; Hasse, Stephan LU ; Bellio, Marie ; Mbarik, Maroua ; Tamagne, Marie ; Allaeys, Isabelle ; Zufferey, Anne ; Lévesque, Tania and Rebetz, Johan LU orcid , et al. (2021) In Blood 138(25). p.2607-2620
Abstract

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... (More)

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.

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publishing date
type
Contribution to journal
publication status
published
subject
keywords
Animals, Antigen Presentation, Blood Platelets/chemistry, Extracellular Vesicles/chemistry, Histocompatibility Antigens Class I/analysis, Humans, Mice, Mice, Inbred C57BL, Proteasome Endopeptidase Complex/analysis
in
Blood
volume
138
issue
25
pages
2607 - 2620
publisher
American Society of Hematology
external identifiers
  • scopus:85116343534
  • pmid:34293122
ISSN
1528-0020
DOI
10.1182/blood.2020009957
language
English
LU publication?
yes
additional info
© 2021 by The American Society of Hematology.
id
943b3241-5042-49d5-9081-67a20c85ec25
date added to LUP
2022-11-09 15:20:10
date last changed
2024-11-12 22:50:22
@article{943b3241-5042-49d5-9081-67a20c85ec25,
  abstract     = {{<p>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.</p>}},
  author       = {{Marcoux, Genevieve and Laroche, Audrée and Hasse, Stephan and Bellio, Marie and Mbarik, Maroua and Tamagne, Marie and Allaeys, Isabelle and Zufferey, Anne and Lévesque, Tania and Rebetz, Johan and Karakeussian-Rimbaud, Annie and Turgeon, Julie and Bourgoin, Sylvain G and Hamzeh-Cognasse, Hind and Cognasse, Fabrice and Kapur, Rick and Semple, John W and Hébert, Marie-Josée and Pirenne, France and Overkleeft, Herman S and Florea, Bogdan I and Dieude, Mélanie and Vingert, Benoît and Boilard, Eric}},
  issn         = {{1528-0020}},
  keywords     = {{Animals; Antigen Presentation; Blood Platelets/chemistry; Extracellular Vesicles/chemistry; Histocompatibility Antigens Class I/analysis; Humans; Mice; Mice, Inbred C57BL; Proteasome Endopeptidase Complex/analysis}},
  language     = {{eng}},
  month        = {{12}},
  number       = {{25}},
  pages        = {{2607--2620}},
  publisher    = {{American Society of Hematology}},
  series       = {{Blood}},
  title        = {{Platelet EVs contain an active proteasome involved in protein processing for antigen presentation via MHC-I molecules}},
  url          = {{http://dx.doi.org/10.1182/blood.2020009957}},
  doi          = {{10.1182/blood.2020009957}},
  volume       = {{138}},
  year         = {{2021}},
}