Abstract Number: PB1668
Meeting: ISTH 2020 Congress
Background: In addition to their role in hemostasis, platelets are also recognized for their contribution in immunity. Like megakaryocytes, platelets contain proteasome and present antigen-MHC class I molecules. Once activated, platelets release extracellular vesicles (PEV) formed by the budding of cytoplasmic membranes. PEVs are heterogeneous in terms of content (e.g. nucleic acid, enzymes, mitochondria) and surface molecules, suggesting that they may play diverse functions. However, whether the proteasome is also transferred and can support protein processing has never been examined.
Aims: We hypothesized that a functional antigen processing and presenting machinery is transferred to PEV by activated platelets.
Methods: Immunoblotting, flow cytometry and an enzymatic activity assay were used to reveal if PEV from activated platelets contains active 20S proteasome and presentation molecules. Ovalbumin antigenic peptide and whole protein were used to determined that PEV could process it through their active proteasome and load antigenic peptide in MHC-I molecule.
Results: These proteasome-containing PEV were found to express MHC-I and lymphocyte co-activation proteins such as CD40L and OX40L. Proteasome-containing PEV exposing MHC-I molecules were identified in blood in healthy volunteers, were increased in inflammatory conditions, and were found in the lymphatic system. Intravenous injection of PEV in mice revealed that they could reach lymphoid organs where they could interact with lymphocytes. In OT-1 mice, all T lymphocyte TCR recognize processed ovalbumin peptide loaded in MHC-I molecule, thereby stimulating these cells to secrete cytokines and to proliferate. Importantly, the co-incubation of PEV and lymphocytes from OT-1 mice led to the production of cytokines and lymphocyte proliferation, a process that was blunted by PEV 20S proteasome inhibition.
Conclusions: Contrarily to platelets, which cannot circulate in lymph, PEV have privileged access to immune cells through the lymphatic system. With their machinery capable of protein processing and antigen presentation, this study reveals a novel role for PEV in immunity.
To cite this abstract in AMA style:Marcoux G, Laroche A, Hasse S, Tamagne M, Tessandier N, Becker YLC, Zufferey A, Levesque T, Allaeys I, Karakeussian-Rimbaud A, Turgeon J, Hamzeh-Cognasse H, Cognasse F, Hébert M-, Bourgoin S, Pirenne F, Overkleeft HS, Dieudé M, Vingert B, Boilard E. Platelet-Derived Extracellular Vesicles Actively Process Proteins and Present Antigen via MHC Class I [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/platelet-derived-extracellular-vesicles-actively-process-proteins-and-present-antigen-via-mhc-class-i/. Accessed February 27, 2024.
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